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Achouri H, Derguini A, Idres T, Selamoglu Z, Hamadi NB, Jalouli M, Elfalleh W, Bendif H, Badraoui R, Boufahja F, Dellali M. Impact of climate change on the toxicity of bisphenol A in Mytilus galloprovincialis and assessment of phycoremediation using Nannochloropsis salina via a multi-biomarker strategy and modeling. MARINE POLLUTION BULLETIN 2025; 216:118010. [PMID: 40253969 DOI: 10.1016/j.marpolbul.2025.118010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2025] [Revised: 04/09/2025] [Accepted: 04/16/2025] [Indexed: 04/22/2025]
Abstract
In the current study, the mussels Mytilus galloprovincialis, exposed to four varying temperatures (17, 20, 23, and 26 °C), were contaminated with 50 μg/L of bisphenol A both with and without Nannochloropsis salina. The toxicity evaluation is determined by quantifying various biomarkers related to oxidative stress, neurotoxicity, and cellular damage. The key findings indicate that the toxicity of bisphenol A is heightened by rising temperature. The impact of bisphenol A is most evident at 26 °C, leading to excessive production of reactive oxygen species, depletion of non-enzymatic antioxidants, and activation of antioxidant enzymes (catalase and glutathione-S-transferase). The rise in malondialdehyde levels confirms lipid peroxidation caused by bisphenol A and intensified by thermal stress. These findings have been supported by strong molecular interactions between bisphenol A and lectin mytilec apo-form and proximal thread matrix protein 1 from M. galloprovincialis following the computational modeling assay. The incorporation of N. salina as a food additive helped, firstly, to mitigate the stress effects and, secondly, resulted in a noticeable enhancement of oxidative balance and filtration ability, along with decreased lipid peroxidation.
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Affiliation(s)
- Haifa Achouri
- University of Carthage, Faculty of Sciences of Bizerte, Laboratory of Environment Biomonitoring, Coastal Ecology and Ecotoxicology Unit, 7021 Zarzouna, Tunisia
| | - Assia Derguini
- Microbial Ecology Laboratory, FSNV, Abderrahmane MIRA University, 06017 Bejaïa, Algeria.
| | - Takfarinas Idres
- Laboratory for Livestock Animal Production and Health Research, Rabie Bouchama National Veterinary School of Algiers, Issad ABBAS Street, BP 161 Oued Semar, Algiers, Algeria.
| | - Zeliha Selamoglu
- Department of Medical Biology, Medicine Faculty, Nigde Omer Halisdemir University, Nigde, Turkey.
| | - Naoufel Ben Hamadi
- Chemistry Department, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Box 5701, Riyadh 11432, Saudi Arabia.
| | - Maroua Jalouli
- Biology Department, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia.
| | - Walid Elfalleh
- Biology Department, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia.
| | - Hamdi Bendif
- Biology Department, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia.
| | - Riadh Badraoui
- Department of Biology, University of Ha'il, Ha'il 45851, Saudi Arabia.
| | - Fehmi Boufahja
- Biology Department, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia.
| | - Mohamed Dellali
- University of Carthage, Faculty of Sciences of Bizerte, Laboratory of Environment Biomonitoring, Coastal Ecology and Ecotoxicology Unit, 7021 Zarzouna, Tunisia.
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Ahmadpourmir H, Moradzehi M, Velayati M, Taghizadeh SF, Hashemzaei M, Rezaee R. Global occurrence of bisphenol compounds in breast milk and infant formula: A systematic review. Food Res Int 2025; 211:116389. [PMID: 40356106 DOI: 10.1016/j.foodres.2025.116389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 03/22/2025] [Accepted: 04/15/2025] [Indexed: 05/15/2025]
Abstract
Bisphenol compounds (BPs), particularly bisphenol A (BPA), are chemicals that are widely used in various industrial sections and come into contact with humans via different routes of exposure. Documented toxic effects of BPs include androgenicity, estrogenecity, cytotoxicity, neurotoxicity, etc. As a well-known member of bisphenols, BPA is an endocrine disruptor chemical (EDC) that has been the subject of safety regulations. Monitoring infants' exposure to BPs via consumption of breast milk and infant formula is essential as they are at critical stages of development and are potentially more vulnerable. Following a systematic search in databases PubMed and Scopus, out of 44 studies included in the present work, 27 and 13 analyzed breast milk and infant formula samples, respectively. In addition, 4 studies reported BPs levels in both matrices. BPA is the most frequently detected BP with concentrations in breast milk reaching up to 112.44 ng/g in samples from Taiwan and as high as 262 ng/g in formula samples from Canada. For breast milk and formula samples, Liquid Chromatography coupled with Tandem Mass Spectrometry (HPLC-MS/MS) and Gas Chromatography Mass Spectrometry (GC-MS) were the most frequently employed methods of detection, respectively. Our review indicates scarcity of data on BPA analogs such as bisphenol S (BPS) and bisphenol F (BPF), highlighting the necessity for assessment of the occurrence of all BPA analogs in these matrices.
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Affiliation(s)
- Hamid Ahmadpourmir
- Medical Toxicology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Masomeh Moradzehi
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran; Toxicology and Addiction Research Center, Zabol University of Medical Sciences, Zabol, Iran
| | - Mahin Velayati
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Mahmoud Hashemzaei
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran; Toxicology and Addiction Research Center, Zabol University of Medical Sciences, Zabol, Iran.
| | - Ramin Rezaee
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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Waleed S, Haroon M, Ullah N, Tuzen M, Rind IK, Sarı A. A comprehensive review on advanced trends in treatment technologies for removal of Bisphenol A from aquatic media. ENVIRONMENTAL MONITORING AND ASSESSMENT 2024; 197:83. [PMID: 39707071 DOI: 10.1007/s10661-024-13460-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 11/26/2024] [Indexed: 12/23/2024]
Abstract
Toxic environmental pollutants are considered to be posed a major threat to human and aquatic systems. The fast advancement of the petrochemical and chemical industries has woken up rising worries concerning the pollution of water by contaminants including phenolic Bisphenol A (BPA), an endocrine-disrupting chemical (EDC). The intermediate BPA used in synthesis of certain plastics, polycarbonate polymers, polysulfone, and epoxy resins of various polyesters. Due to potential health risks, severe toxicity, and widespread distribution, there is an urgent need to develop efficient techniques for the removal of BPA. Therefore, advance management for the active elimination of BPA prior to its release into the water sources is of serious concern. Degradation, membrane separation, adsorption, and biological treatments have been extensively examined as they are easy to operate and cost-effective for effective BPA removal. In this review, we summarized the mechanism and performance for removal of BPA by several sorbents, including natural polymers, natural inorganic minerals, porous and carbon-based materials. Comparative results revealed that composite materials and modified adsorbents have good performances for removal of BPA. Furthermore, kinetic study investigating adsorption mechanisms was also discussed. Hazardous quantities of such types of chemicals in various samples have thus been the subject of increasing concern of investigation. This review clarified the extensive literature regarding the major health effects of BPA and its advanced treatment technologies including biological treatment by natural and synthetic materials have been discussed briefly. It delivers regulation for future development and research from the aspects of materials functionalization, development of methods, and mechanism investigation that directing to stimulate developments for removal of emerging contaminants.
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Affiliation(s)
- Sangeen Waleed
- Department of Chemistry, University of Gwadar, Balochistan, 92600, Pakistan
| | - Muhammad Haroon
- Department of Chemistry, University of Gwadar, Balochistan, 92600, Pakistan
| | - Naeem Ullah
- Department of Chemistry, University of Gwadar, Balochistan, 92600, Pakistan
- Faculty of Science and Arts, Chemistry Department, Tokat Gaziosmanpaşa University, 60250, Tokat, Turkey
| | - Mustafa Tuzen
- Faculty of Science and Arts, Chemistry Department, Tokat Gaziosmanpaşa University, 60250, Tokat, Turkey
| | - Imran Khan Rind
- National Centre of Excellence in Analytical Chemistry, University of Sindh, Jamshoro, Pakistan.
- Department of Metallurgical and Material Engineering, Karadeniz Technical University, 61080, Trabzon, Turkey.
| | - Ahmet Sarı
- Department of Metallurgical and Material Engineering, Karadeniz Technical University, 61080, Trabzon, Turkey
- Interdisciplinary Research Center of Renewable Energy and Power Systems (IRC-REPS), King Fahd University of Petroleum & Minerals, Dhahran, Saudi Arabia
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Ahmad S, Akmal H, Shahzad K, Ahmad Khan MK, Jabeen F. Evaluating the Toxicity Induced by Bisphenol F in Labeo rohita Fish Using Multiple Biomarker Approach. SCIENTIFICA 2024; 2024:8646751. [PMID: 39555222 PMCID: PMC11567727 DOI: 10.1155/2024/8646751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 06/01/2024] [Accepted: 06/28/2024] [Indexed: 11/19/2024]
Abstract
Bisphenol F (BPF) is an emerging contaminant extensively used in the pharmaceutical, chemical, and food industries, exerting deleterious effects on human and wildlife health. Therefore, the current study was conducted to assess the toxicity induced by BPF in rohu Labeo rohita using multiple biomarkers such as oxidative stress, activity of antioxidant enzymes, biochemical parameters, histology, and genotoxicity. Fish were separated into four groups (T1-T4). Group T1 served as a control (0 μg/L), while Groups T2, T3, and T4 were exposed to BPF concentrations of 600 μg/L, 1200 μg/L, and 1800 μg/L, respectively, for 21 days. Results showed a significant (p < 0.05) increase in oxidative biomarkers (thiobarbituric acid reactive substance [TBARS] and reactive oxygen species [ROS]), while the concentration of antioxidant biomarkers (peroxidase [POD], superoxide dismutase [SOD], reduced glutathione [GSH], and catalase) was significantly (p < 0.05) decreased with the rising concentration of BPF in the liver, gills, and kidney of fish. Significant reduction (p < 0.05) in biochemical parameters was measured from collected whole blood, including red blood cells (RBCs), hemoglobin (HGB), mean corpuscular HGB (MCH), MC volume (MCV), hematocrit (HCT), MC HGB concentration (MCHC), platelets, low-density lipoprotein (LDL), cholesterol, high-density lipoprotein (HDL), total proteins, very LDL (VLDL), albumin and globulin, while white blood cells (WBCs), neutrophils, triglycerides, aspartate aminotransferase (AST), blood glucose, and alanine transaminase (ALT) levels were increased significantly (p < 0.05). Comet assay showed the DNA damage potential of BPF in erythrocytes. Histological examination showed that exposure to BPF causes several degenerative effects in the soft tissues (gills, liver, and kidney) of treated fish. It is concluded that BPF induces deleterious effects via disruptions in histological, genotoxic, and biochemical alterations in several organs of exposed fish.
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Affiliation(s)
- Shabbir Ahmad
- Department of Zoology, University of Okara, Okara 56130, Pakistan
| | - Hasnain Akmal
- Department of Zoology, University of Okara, Okara 56130, Pakistan
| | - Khurram Shahzad
- Department of Zoology, University of Okara, Okara 56130, Pakistan
| | | | - Farhat Jabeen
- Department of Zoology, Government College University Faisalabad, Faisalabad 37251, Pakistan
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Kim SH, Kang DW, Kwon D, Jung YS. Critical role of endoplasmic reticulum stress on bisphenol A-induced cytotoxicity in human keratinocyte HaCaT cells. ENVIRONMENTAL TOXICOLOGY 2024; 39:4091-4104. [PMID: 38629620 DOI: 10.1002/tox.24290] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 03/04/2024] [Accepted: 03/31/2024] [Indexed: 07/14/2024]
Abstract
Bisphenol A (BPA) is widely used in plastic and paper products, and its exposure can occur through skin contact or oral ingestion. The hazardous effects of BPA absorbed through the skin may be more severe; however, few studies have investigated the skin toxicity of BPA. This study investigated the effects of BPA on human epidermal keratinocyte cell lines, which is relevant for skin exposure. BPA treatment reduced cell viability in a time- and concentration-dependent manner and elevated oxidative and endoplasmic reticulum (ER) stress. N-acetylcysteine (NAC), an oxidative stress inhibitor, reduced BPA-induced reactive oxygen species (ROS) levels. However, only 10% of the decreased cell viability was restored at the highest NAC concentration. Treatment with tauroursodeoxycholic acid (TUDCA), which is an ER stress inhibitor, effectively countered the increase in ER stress-related proteins induced by BPA. Moreover, TUDCA treatment led to a reduction in oxidative stress, as demonstrated by the decrease in ROS levels, maintenance of mitochondrial membrane potential, and modulation of stress signaling proteins. Consequently, TUDCA significantly improved BPA-induced cytotoxicity in a concentration-dependent manner. Notably, combined treatment using TUDCA and NAC further reduced the BPA-induced ROS levels; however, no significant difference in cell viability was observed compared with that for TUDCA treatment alone. These findings indicated that the oxidative stress observed following BPA exposure was exacerbated by ER stress. Moreover, the principal factor driving BPA-induced cytotoxicity was indeed ER stress, which has potential implications for developing therapeutic strategies for diseases associated with similar stress responses.
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Affiliation(s)
- Sou Hyun Kim
- Department of Pharmacy, College of Pharmacy, Research Institute for Drug Development, Pusan National University, Busan, Republic of Korea
| | - Dong Wan Kang
- Department of Pharmacy, College of Pharmacy, Research Institute for Drug Development, Pusan National University, Busan, Republic of Korea
| | - Doyoung Kwon
- College of Pharmacy, Jeju Research Institute of Pharmaceutical Sciences, Jeju National University, Jeju, Republic of Korea
| | - Young-Suk Jung
- Department of Pharmacy, College of Pharmacy, Research Institute for Drug Development, Pusan National University, Busan, Republic of Korea
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Lința AV, Lolescu BM, Ilie CA, Vlad M, Blidișel A, Sturza A, Borza C, Muntean DM, Crețu OM. Liver and Pancreatic Toxicity of Endocrine-Disruptive Chemicals: Focus on Mitochondrial Dysfunction and Oxidative Stress. Int J Mol Sci 2024; 25:7420. [PMID: 39000526 PMCID: PMC11242905 DOI: 10.3390/ijms25137420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 06/29/2024] [Accepted: 07/02/2024] [Indexed: 07/16/2024] Open
Abstract
In recent years, the worldwide epidemic of metabolic diseases, namely obesity, metabolic syndrome, diabetes and metabolic-associated fatty liver disease (MAFLD) has been strongly associated with constant exposure to endocrine-disruptive chemicals (EDCs), in particular, the ones able to disrupt various metabolic pathways. EDCs have a negative impact on several human tissues/systems, including metabolically active organs, such as the liver and pancreas. Among their deleterious effects, EDCs induce mitochondrial dysfunction and oxidative stress, which are also the major pathophysiological mechanisms underlying metabolic diseases. In this narrative review, we delve into the current literature on EDC toxicity effects on the liver and pancreatic tissues in terms of impaired mitochondrial function and redox homeostasis.
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Affiliation(s)
- Adina V. Lința
- Department of Functional Sciences—Chair of Pathophysiology, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, E. Murgu Sq. No. 2, 300041 Timișoara, Romania; (A.V.L.); (A.S.); (C.B.)
- Centre for Translational Research and Systems Medicine, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, E. Murgu Sq. No. 2, 300041 Timișoara, Romania; (B.M.L.); (C.A.I.)
- Doctoral School Medicine-Pharmacy, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, E. Murgu Sq., No. 2, 300041 Timișoara, Romania
| | - Bogdan M. Lolescu
- Centre for Translational Research and Systems Medicine, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, E. Murgu Sq. No. 2, 300041 Timișoara, Romania; (B.M.L.); (C.A.I.)
- Doctoral School Medicine-Pharmacy, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, E. Murgu Sq., No. 2, 300041 Timișoara, Romania
| | - Cosmin A. Ilie
- Centre for Translational Research and Systems Medicine, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, E. Murgu Sq. No. 2, 300041 Timișoara, Romania; (B.M.L.); (C.A.I.)
- Department of Functional Sciences—Chair of Public Health & Sanitary Management, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, E. Murgu Sq. No. 2, 300041 Timișoara, Romania
| | - Mihaela Vlad
- Department of Internal Medicine II—Chair of Endocrinology, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, E. Murgu Sq., No. 2, 300041 Timișoara, Romania;
| | - Alexandru Blidișel
- Department of Surgery I—Chair of Surgical Semiotics & Thoracic Surgery, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, E. Murgu Sq. No. 2, 300041 Timişoara, Romania; (A.B.); (O.M.C.)
- Centre for Hepato-Biliary and Pancreatic Surgery, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, E. Murgu Sq. No. 2, 300041 Timişoara, Romania
| | - Adrian Sturza
- Department of Functional Sciences—Chair of Pathophysiology, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, E. Murgu Sq. No. 2, 300041 Timișoara, Romania; (A.V.L.); (A.S.); (C.B.)
- Centre for Translational Research and Systems Medicine, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, E. Murgu Sq. No. 2, 300041 Timișoara, Romania; (B.M.L.); (C.A.I.)
| | - Claudia Borza
- Department of Functional Sciences—Chair of Pathophysiology, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, E. Murgu Sq. No. 2, 300041 Timișoara, Romania; (A.V.L.); (A.S.); (C.B.)
- Centre for Translational Research and Systems Medicine, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, E. Murgu Sq. No. 2, 300041 Timișoara, Romania; (B.M.L.); (C.A.I.)
| | - Danina M. Muntean
- Department of Functional Sciences—Chair of Pathophysiology, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, E. Murgu Sq. No. 2, 300041 Timișoara, Romania; (A.V.L.); (A.S.); (C.B.)
- Centre for Translational Research and Systems Medicine, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, E. Murgu Sq. No. 2, 300041 Timișoara, Romania; (B.M.L.); (C.A.I.)
| | - Octavian M. Crețu
- Department of Surgery I—Chair of Surgical Semiotics & Thoracic Surgery, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, E. Murgu Sq. No. 2, 300041 Timişoara, Romania; (A.B.); (O.M.C.)
- Centre for Hepato-Biliary and Pancreatic Surgery, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, E. Murgu Sq. No. 2, 300041 Timişoara, Romania
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Lu X, Yu M, Yang Y, Zhang X, Chen T, Lei B. G-Protein Coupled Receptor 1 Is Involved in Tetrachlorobisphenol A-Induced Inflammatory Response in Jurkat Cells. TOXICS 2024; 12:485. [PMID: 39058137 PMCID: PMC11281156 DOI: 10.3390/toxics12070485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 06/21/2024] [Accepted: 06/29/2024] [Indexed: 07/28/2024]
Abstract
Estrogens can affect the immune inflammatory response through estrogen receptor alpha (ERα), but the specific role of estrogen member receptor G-protein coupled receptor 1 (GPER1) in this process remains unclear. In this study, we evaluated the effects of tetrachlorobisphenol A (TCBPA), which has estrogen activity, on immune inflammatory-related indicators of Jurkat cells, as well as investigated the role of GPER1 in these effects. The results showed that TCBPA at lower concentrations significantly promoted the viability of Jurkat cells, whereas higher concentrations decreased cell viability. TCBPA at concentrations ranging from 1 to 25 μM increased the intracellular reactive oxygen species (ROS) levels. Additionally, treatment with 10 μM TCBPA increased the protein expression of ERα and GPER1, elevated the phosphorylation of protein kinase B (p-Akt), and upregulated the mRNA levels of GPER1, Akt, and phosphoinositide 3-kinase (PI3K) genes. Treatment with 10 μM TCBPA also upregulated the protein or gene expression of pro-inflammatory cytokines, such as interleukins (IL1β, IL2, IL6, IL8, IL12α) and tumor necrosis factor alpha (TNFα) in Jurkat cells. Furthermore, pretreatment with a GPER1 inhibitor G15 significantly reduced the mRNA levels of Akt induced by 10 μM TCBPA. Moreover, the upregulation of mRNA expression of RelA (p65), TNFα, IL6, IL8, and IL12α induced by 10 μM TCBPA was also significantly attenuated after G15 pretreatment. These findings suggest that TCBPA upregulates the expression of genes related to inflammatory responses by activating the GPER1-mediated PI3K/Akt signaling pathway. This study provides new insights into the mechanism of TCBPA-induced inflammatory response.
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Affiliation(s)
- Xiaoyu Lu
- Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China; (X.L.); (M.Y.); (Y.Y.); (X.Z.)
| | - Mengjie Yu
- Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China; (X.L.); (M.Y.); (Y.Y.); (X.Z.)
| | - Yingxin Yang
- Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China; (X.L.); (M.Y.); (Y.Y.); (X.Z.)
| | - Xiaolan Zhang
- Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China; (X.L.); (M.Y.); (Y.Y.); (X.Z.)
| | - Tian Chen
- Department of Environmental Health, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China
- State Environmental Protection Key Laboratory of the Assessment of Effects of Emerging Pollutants on Environmental and Human Health, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China
- NMPA Key Laboratory for Monitoring and Evaluation of Cosmetics, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China
| | - Bingli Lei
- Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China; (X.L.); (M.Y.); (Y.Y.); (X.Z.)
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Ahmad I, Kaur M, Tyagi D, Singh TB, Kaur G, Afzal SM, Jauhar M. Exploring novel insights into the molecular mechanisms underlying Bisphenol A-induced toxicity: A persistent threat to human health. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2024; 108:104467. [PMID: 38763439 DOI: 10.1016/j.etap.2024.104467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 04/09/2024] [Accepted: 05/11/2024] [Indexed: 05/21/2024]
Abstract
Bisphenol A (BPA) is a ubiquitous industrial chemical used in the production of polycarbonate plastics and epoxy resins, found in numerous consumer products. Despite its widespread use, its potential adverse health effects have raised significant concerns. This review explores the molecular mechanisms and evidence-based literature underlying BPA-induced toxicities and its implications for human health. BPA is an endocrine-disrupting chemical (EDC) which exhibits carcinogenic properties by influencing various receptors, such as ER, AhR, PPARs, LXRs, and RARs. It induces oxidative stress and contributes to cellular dysfunction, inflammation, and DNA damage, ultimately leading to various toxicities including but not limited to reproductive, cardiotoxicity, neurotoxicity, and endocrine toxicity. Moreover, BPA can modify DNA methylation patterns, histone modifications, and non-coding RNA expression, leading to epigenetic changes and contribute to carcinogenesis. Overall, understanding molecular mechanisms of BPA-induced toxicity is crucial for developing effective strategies and policies to mitigate its adverse effects on human health.
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Affiliation(s)
- Israel Ahmad
- Department of Pharmacology, School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T. Road, Phagwara, Punjab, India.
| | - Mandeep Kaur
- Department of Pharmacology, School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T. Road, Phagwara, Punjab, India.
| | - Devansh Tyagi
- Department of Pharmacology, School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T. Road, Phagwara, Punjab, India.
| | - Tejinder Bir Singh
- Department of Pharmacology, School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T. Road, Phagwara, Punjab, India.
| | - Gurpreet Kaur
- School of Business Studies, Punjab Agricultural University, Ludhiana, Punjab, India.
| | - Shaikh Mohammad Afzal
- Department of Pharmacology, School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T. Road, Phagwara, Punjab, India.
| | - Mohsin Jauhar
- Department of Pharmacology, School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T. Road, Phagwara, Punjab, India.
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Yang X, Zhou Y, Yu T, Li K, Xu S. TAN (tannic acid) inhibits BPA-induced pyroptosis of L8824 (grass carp hepatocytes) by regulating PTEN/PI3K/AKT pathway. FISH & SHELLFISH IMMUNOLOGY 2024; 146:109384. [PMID: 38246267 DOI: 10.1016/j.fsi.2024.109384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Revised: 01/13/2024] [Accepted: 01/15/2024] [Indexed: 01/23/2024]
Abstract
Bisphenol A (BPA) and its analogues are still one of the most important substances that pollute aquatic systems and pose a threat to aquatic organisms. Tannic acid (TAN) is a kind of glycosyl compound, which has the functions of anti-oxidation, anti-inflammation and anti-apoptosis. However, it is unknown if BPA can regulate PTEN/PI3K/AKT pathway to induce pyroptosis of grass carp hepatocytes (L8824) and the antagonistic effect of tannic acid (TAN) through oxidative stress. Therefore, we established the grass carp hepatocytes (L8824) cell model treated with BPA. The oxidative stress indexes (SOD, CAT, GSH, H2O2 and T-AOC) were detected by oxidative stress kit, mRNA and protein expression of associated genes were examined using qRT-PCR and western blotting. The results showed that BPA treatment increased the content of hydrogen peroxide and decreased the activities of antioxidant enzymes and antioxidants (SOD, CAT, GSH, and T-AOC) in L8824 cells. We also found that PTEN/PI3K/AKT pathway was activated dramatically and the expression of pyroptosis-related genes (GSDMD, NLRP3, Caspase1, ASC and IL-1β) was increased significantly. In addition, TAN could significantly reduce the toxicity of BPA on L8824 cells. After the addition of PTEN specific inhibitor SF1670, the activation of PTEN/PI3K/AKT pathway decreased by BPA was inhibited and the expression of scorch related genes was decreased. On the whole, TAN inhibits BPA-induced pyroptosis of L8824 by modulating the PTEN/PI3K/AKT pathway. The present study provides a novel perspective for toxicological mechanism of BPA, and new insights into the detoxification mechanism of TAN.
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Affiliation(s)
- Xuejiao Yang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China
| | - Yuanxin Zhou
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China
| | - Tingting Yu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China
| | - Ke Li
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China
| | - Shiwen Xu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China.
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10
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Ismael LQ, Keong YY, Bahari H, Lan CA, Yin KB. Bombesin-like receptor 3 expression induced by bisphenol A is likely associated with reduced cell proliferation by inhibiting DNA synthesis and inducing inflammation in liver cells. Mol Biol Rep 2024; 51:271. [PMID: 38302795 DOI: 10.1007/s11033-023-09080-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 11/29/2023] [Indexed: 02/03/2024]
Abstract
BACKGROUND Bisphenol A (BPA) is an exogenous endocrine disruptor mimicking hormones closely associated with health complications, such as cancer progression. BPA is also related to an increase in the prevalence of obesity-related diseases due to its obesogenic action. Bombesin-like receptor 3 (BRS3) is an important factor that should be considered in the adipogenic gene network, as depletion of this gene alters adiposity. METHODS Therefore, the present study aimed to investigate the messenger ribonucleic acid (mRNA) expression of BRS3 in human liver THLE-2 cells post-BPA treatment by real-time polymerase chain reaction. The effects of BPA on the levels of pro-inflammatory proteins, interleukin 6 (IL6) and CC motif chemokine ligand 2 (CCL2), in conditioned media of BPA-treated THLE-2 cells and deoxyribonucleic acid (DNA) synthesis in replicating BPA-treated THLE-2 cells during the cell cycle were also examined by enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. RESULTS The study found that the mRNA expression of BRS3 was increased in THLE-2 cells treated with BPA. The study also showed that the expression levels of IL6 and CCL2 reached an optimum level in the conditioned media of BPA-treated THLE-2 cells after 48 h of treatment. Subsequently, the DNA synthesis analysis showed that bromodeoxyuridine/propidium iodide (BrdU/PI) stained positive cells were decreased in BPA-treated THLE-2 cells at 72 h of treatment. CONCLUSION The study demonstrates that BRS3 expression induced by BPA is likely associated with reduced cell proliferation by inhibiting DNA synthesis and inducing cellular inflammation in liver cells.
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Affiliation(s)
- Layla Qasim Ismael
- Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), 11800, USM, Penang, Malaysia
- Department of Medical Biochemical Analysis, Cihan University-Erbil, Erbil, 44001, Iraq
| | - Yong Yoke Keong
- Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Seri Kembangan, 43400, Serdang, Selangor, Malaysia
| | - Hasnah Bahari
- Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Seri Kembangan, 43400, Serdang, Selangor, Malaysia
| | - Chew Ai Lan
- Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), 11800, USM, Penang, Malaysia
| | - Khoo Boon Yin
- Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), 11800, USM, Penang, Malaysia.
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Siddique R, Mehmood MH, Shehzad MA. Current antioxidant medicinal regime and treatments used to alleviate oxidative stress in infertility issues. FUNDAMENTAL PRINCIPLES OF OXIDATIVE STRESS IN METABOLISM AND REPRODUCTION 2024:287-315. [DOI: 10.1016/b978-0-443-18807-7.00018-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Nagarajan M, Maadurshni GB, Manivannan J. Exposure to low dose of Bisphenol A (BPA) intensifies kidney oxidative stress, inflammatory factors expression and modulates Angiotensin II signaling under hypertensive milieu. J Biochem Mol Toxicol 2024; 38:e23533. [PMID: 37718616 DOI: 10.1002/jbt.23533] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 07/18/2023] [Accepted: 09/01/2023] [Indexed: 09/19/2023]
Abstract
Humans are constantly exposed to low concentrations of ubiquitous environmental pollutant, Bisphenol A (BPA). Due to the prevalence of hypertension (one of the major risk factors of cardiovascular disease [CVD]) in the population, it is necessary to explore the adverse effect of BPA under hypertension associated pathogenic milieu. The current study exposed the Nω-nitro-l-arginine methyl ester (L-NAME) induced hypertensive Wistar rats to low dose BPA (50 μg/kg) for 30 days period. In tissue samples immunohistochemistry, real-time quantitative polymerase chain reaction and enzymatic assays were conducted. Moreover, studies on primary kidney cell culture were employed to explore the impact of low dose of BPA exposure at nanomolar level (20-80 nM range) on renal cells through various fluorescence assays. The observed results illustrate that BPA exposure potentiates/aggravates hypertension induced tissue abnormalities (renal fibrosis), oxidative stress (ROS generation), elevated angiotensin-converting enzyme activity, malfunction of the antioxidant and tricarboxylic acid cycle enzymes, tissue lipid abnormalities and inflammatory factor expression (both messenger RNA and protein level of TNF-α and IL-6). Further, in vitro exposure of nM levels of BPA to primary kidney cells modulates oxidative stress (both superoxide and total ROS), mitochondrial physiology (reduced mitochondrial transmembrane potential-∆ψm) and lipid peroxidation in a dose dependent manner. In addition, angiotensin II induced ROS generation was aggravated further by BPA during coexposure in kidney cells. Therefore, during risk assessment, a precise investigation on BPA exposure in hypertensive (CVD vulnerable) populations is highly suggested.
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Affiliation(s)
- Manigandan Nagarajan
- Environmental Health and Toxicology Laboratory, Department of Environmental Sciences, School of Life Sciences, Bharathiar University, Coimbatore, Tamil Nadu, India
| | | | - Jeganathan Manivannan
- Environmental Health and Toxicology Laboratory, Department of Environmental Sciences, School of Life Sciences, Bharathiar University, Coimbatore, Tamil Nadu, India
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Nagarajan M, Maadurshni GB, Manivannan J. Bisphenol A (BPA) exposure aggravates hepatic oxidative stress and inflammatory response under hypertensive milieu - Impact of low dose on hepatocytes and influence of MAPK and ER stress pathways. Food Chem Toxicol 2024; 183:114197. [PMID: 38029875 DOI: 10.1016/j.fct.2023.114197] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 10/27/2023] [Accepted: 11/16/2023] [Indexed: 12/01/2023]
Abstract
Human exposure to the hazardous chemical, Bisphenol A (BPA), is almost ubiquitous. Due to the prevalence of hypertension (CVD risk factor) in the aged human population, it is necessary to explore its adverse effect in hypertensive subjects. The current study exposed the Nω-nitro-l-arginine methyl ester (L-NAME) induced hypertensive Wistar rats to human exposure relevant low dose of BPA (50 μg/kg) for 30 days period. The liver biochemical parameters, histopathology, immunohistochemistry, gene expression (RT-qPCR), trace elements (ICP-MS), primary rat hepatocytes cell culture and metabolomic (1H NMR) assessments were performed. Results illustrate that BPA exposure potentiates/aggravates hypertension induced tissue abnormalities (hepatic fibrosis), oxidative stress, ACE activity, malfunction of the antioxidant system, lipid abnormalities and inflammatory factor (TNF-α and IL-6) expression. Also, in cells, BPA increased ROS generation, mitochondrial dysfunction and lipid peroxidation without any impact on cytotoxicity and caspase 3 and 9 activation. Notably, BPA exposure modulate lipid metabolism (cholesterol and fatty acid) in primary hepatocytes. Finally, the influence of ERK1/2, p38MAPK, ER stress and oxidative stress during relatively high dose of BPA elicited cytotoxicity was observed. Therefore, a precise hazardous risk investigation of BPA exposure in hypertensive populations is highly recommended.
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Affiliation(s)
- Manikandan Nagarajan
- Environmental Health and Toxicology Laboratory, Department of Environmental Sciences, School of Life Sciences, Bharathiar University, Coimbatore, Tamil Nadu, India
| | | | - Jeganathan Manivannan
- Environmental Health and Toxicology Laboratory, Department of Environmental Sciences, School of Life Sciences, Bharathiar University, Coimbatore, Tamil Nadu, India.
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Khan NG, Tungekar B, Adiga D, Chakrabarty S, Rai PS, Kabekkodu SP. Alterations induced by Bisphenol A on cellular organelles and potential relevance on human health. BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR CELL RESEARCH 2023; 1870:119505. [PMID: 37286138 DOI: 10.1016/j.bbamcr.2023.119505] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 04/29/2023] [Accepted: 05/26/2023] [Indexed: 06/09/2023]
Abstract
Bisphenol A (BPA) is a chemical partially soluble in water and exists in a solid state. Its structural similarity with estrogen makes it an endocrine-disrupting chemical. BPA can disrupt signaling pathways at very low doses and may cause organellar stress. According to in vitro and in vivo studies, BPA interacts with various cell surface receptors to cause organellar stress, producing free radicals, cellular toxicity, structural changes, DNA damage, mitochondrial dysfunction, cytoskeleton remodeling, centriole duplication, and aberrant changes in several cell signaling pathways. The current review summarizes the impact of BPA exposure on the structural and functional aspects of subcellular components of cells such as the nucleus, mitochondria, endoplasmic reticulum, lysosome, ribosome, Golgi apparatus, and microtubules and its consequent impact on human health.
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Affiliation(s)
- Nadeem G Khan
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
| | - Bushra Tungekar
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
| | - Divya Adiga
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
| | - Sanjiban Chakrabarty
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India; Center for DNA Repair and Genome Stability (CDRGS), Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
| | - Padmalatha S Rai
- Department of Biotechnology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
| | - Shama Prasada Kabekkodu
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India; Center for DNA Repair and Genome Stability (CDRGS), Manipal Academy of Higher Education, Manipal, Karnataka 576104, India.
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Muzeza C, Ngole-Jeme V, Msagati TAM. The Mechanisms of Plastic Food-Packaging Monomers' Migration into Food Matrix and the Implications on Human Health. Foods 2023; 12:3364. [PMID: 37761073 PMCID: PMC10529129 DOI: 10.3390/foods12183364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 08/19/2023] [Accepted: 08/23/2023] [Indexed: 09/29/2023] Open
Abstract
The development of packaging technology has become a crucial part of the food industry in today's modern societies, which are characterized by technological advancements, industrialization, densely populated cities, and scientific advancements that have increased food production over the past 50 years despite the lack of agricultural land. Various types of food-packaging materials are utilized, with plastic being the most versatile. However, there are certain concerns with regards to the usage of plastic packaging because of unreacted monomers' potential migration from the polymer packaging to the food. The magnitude of monomer migration depends on numerous aspects, including the monomer chemistry, type of plastic packaging, physical-chemical parameters such as the temperature and pH, and food chemistry. The major concern for the presence of packaging monomers in food is that some monomers are endocrine-disrupting compounds (EDCs) with a capability to interfere with the functioning of vital hormonal systems in the human body. For this reason, different countries have resolved to enforce guidelines and regulations for packaging monomers in food. Additionally, many countries have introduced migration testing procedures and safe limits for packaging monomer migration into food. However, to date, several research studies have reported levels of monomer migration above the set migration limits due to leaching from the food-packaging materials into the food. This raises concerns regarding possible health effects on consumers. This paper provides a critical review on plastic food-contact materials' monomer migration, including that from biodegradable plastic packaging, the monomer migration mechanisms, the monomer migration chemistry, the key factors that affect the migration process, and the associated potential EDC human health risks linked to monomers' presence in food. The aim is to contribute to the existing knowledge and understanding of plastic food-packaging monomer migration.
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Affiliation(s)
- Celia Muzeza
- Institute for Nanotechnology and Water Sustainability (iNanoWS), College of Science, Engineering and Technology, University of South Africa, Science Campus, Roodepoort, Johannesburg 1709, South Africa
- Department of Environmental Science, College of Agriculture and Environmental Sciences, University of South Africa, Science Campus, Roodepoort, Johannesburg 1709, South Africa;
| | - Veronica Ngole-Jeme
- Department of Environmental Science, College of Agriculture and Environmental Sciences, University of South Africa, Science Campus, Roodepoort, Johannesburg 1709, South Africa;
| | - Titus Alfred Makudali Msagati
- Institute for Nanotechnology and Water Sustainability (iNanoWS), College of Science, Engineering and Technology, University of South Africa, Science Campus, Roodepoort, Johannesburg 1709, South Africa
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Chakraborty S, Anand S, Coe S, Reh B, Bhandari RK. The PCOS-NAFLD Multidisease Phenotype Occurred in Medaka Fish Four Generations after the Removal of Bisphenol A Exposure. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2023; 57:12602-12619. [PMID: 37581432 PMCID: PMC10469501 DOI: 10.1021/acs.est.3c01922] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 07/17/2023] [Accepted: 07/18/2023] [Indexed: 08/16/2023]
Abstract
As a heterogeneous reproductive disorder, polycystic ovary syndrome (PCOS) can be caused by genetic, diet, and environmental factors. Bisphenol A (BPA) can induce PCOS and nonalcoholic fatty liver disease (NAFLD) due to direct exposure; however, whether these phenotypes persist in future unexposed generations is not currently understood. In a previous study, we observed that transgenerational NAFLD persisted in female medaka for five generations (F4) after exposure to an environmentally relevant concentration (10 μg/L) of BPA. Here, we demonstrate PCOS in the same F4 generation female medaka that developed NAFLD. The ovaries contained immature follicles, restricted follicular progression, and degenerated follicles, which are characteristics of PCOS. Untargeted metabolomic analysis revealed 17 biomarkers in the ovary of BPA lineage fish, whereas transcriptomic analysis revealed 292 genes abnormally expressed, which were similar to human patients with PCOS. Metabolomic-transcriptomic joint pathway analysis revealed activation of the cancerous pathway, arginine-proline metabolism, insulin signaling, AMPK, and HOTAIR regulatory pathways, as well as upstream regulators esr1 and tgf signaling in the ovary. The present results suggest that ancestral BPA exposure can lead to PCOS phenotypes in the subsequent unexposed generations and warrant further investigations into potential health risks in future generations caused by initial exposure to EDCs.
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Affiliation(s)
- Sourav Chakraborty
- Department of Biology, University of North Carolina at Greensboro, Greensboro 27412 North Carolina, United
States
| | - Santosh Anand
- Department of Biology, University of North Carolina at Greensboro, Greensboro 27412 North Carolina, United
States
| | - Seraiah Coe
- Department of Biology, University of North Carolina at Greensboro, Greensboro 27412 North Carolina, United
States
| | - Beh Reh
- Department of Biology, University of North Carolina at Greensboro, Greensboro 27412 North Carolina, United
States
| | - Ramji Kumar Bhandari
- Department of Biology, University of North Carolina at Greensboro, Greensboro 27412 North Carolina, United
States
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Odetayo AF, Adeyemi WJ, Olayaki LA. In vivo exposure to bisphenol F induces oxidative testicular toxicity: role of Erβ and p53/Bcl-2 signaling pathway. FRONTIERS IN REPRODUCTIVE HEALTH 2023; 5:1204728. [PMID: 37601897 PMCID: PMC10433915 DOI: 10.3389/frph.2023.1204728] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 07/07/2023] [Indexed: 08/22/2023] Open
Abstract
Introduction Bisphenol F (BPF), an alternative to bisphenol A has been implicated as a gonadotoxic substance. BPF has been shown to induce hormonal imbalance and testicular oxidative damage. However, the mechanism associated with BPF-induced testicular toxicity has not been fully explored. This study was designed to explore the role of tumor protein (p53)/ B-cell lymphoma 2 (BCl-2) signaling and oestrogen receptor beta (Erβ) in BPF-induced testicular toxicity. Methods Male Wistar rats were randomized into control (Cntrl), BPF-treated (10, 30, and 50 mg/kg for low dose (BPF-L), medium dose (BPF-M), and high dose (BPF-H) respectively), and BPF-treated recovery (Cntrl-R, BPF-L-R, BPF-M-R, and BPF-H-R). The administration was via gavage and lasted for 28 days and the animals in the recovery groups were allowed 28-days exposure free period for recovery from BPF exposure. Results BPF resulted in the distortion of the testicular histoarchitecture, which was accompanied by a significant rise in testicular gamma-lutamyl transferase and lactate dehydrogenase activities but a decline in sorbitol dehydrogenase activities. Also, BPF caused a significant reduction in plasma gonadotropin-releasing hormone, luteinising hormone, follicle-stimulating hormone, and testosterone, which was associated with the downregulation of testicular 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase activities. Furthermore, BPF induced testicular inflammation, redox imbalance, and apoptosis, accompanied by distortion in p53/BCl-2 signaling and overexpression of Erβ. Again, the observed toxic effects of BPF were dose-dependent and not completely reversed by BPF cessation. Discussion Bisphenol F induced gonadotoxicity by distorting p53/BCl2 signaling and the expression of Erβ. These observed alterations were not completely reversed after the cessation of BPF exposure.
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Affiliation(s)
- Adeyemi Fatai Odetayo
- Physiology Department, University of Ilorin, Ilorin, Nigeria
- Physiology Department, Federal University of Health Sciences, Ila Orangun, Nigeria
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Milanović M, Milošević N, Milić N, Stojanoska MM, Petri E, Filipović JM. Food contaminants and potential risk of diabetes development: A narrative review. World J Diabetes 2023; 14:705-723. [PMID: 37383596 PMCID: PMC10294057 DOI: 10.4239/wjd.v14.i6.705] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 03/03/2023] [Accepted: 04/13/2023] [Indexed: 06/14/2023] Open
Abstract
The number of people diagnosed with diabetes continues to increase, especially among younger populations. Apart from genetic predisposition and lifestyle, there is increasing scientific and public concern that environmental agents may also contribute to diabetes. Food contamination by chemical substances that originate from packaging materials, or are the result of chemical reactions during food processing, is generally recognized as a worldwide problem with potential health hazards. Phthalates, bisphenol A (BPA) and acrylamide (AA) have been the focus of attention in recent years, due to the numerous adverse health effects associated with their exposure. This paper summarizes the available data about the association between phthalates, BPA and AA exposure and diabetes. Although their mechanism of action has not been fully clarified, in vitro, in vivo and epidemiological studies have made significant progress toward identifying the potential roles of phthalates, BPA and AA in diabetes development and progression. These chemicals interfere with multiple signaling pathways involved in glucose and lipid homeostasis and can aggravate the symptoms of diabetes. Especially concerning are the effects of exposure during early stages and the gestational period. Well-designed prospective studies are needed in order to better establish prevention strategies against the harmful effects of these food contaminants.
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Affiliation(s)
- Maja Milanović
- Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Novi Sad 21000, Serbia
| | - Nataša Milošević
- Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Novi Sad 21000, Serbia
| | - Nataša Milić
- Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Novi Sad 21000, Serbia
| | - Milica Medić Stojanoska
- Faculty of Medicine, Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Vojvodina, University of Novi Sad, Novi Sad 21000, Serbia
| | - Edward Petri
- Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad 21000, Serbia
| | - Jelena Marković Filipović
- Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad 21000, Serbia
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Cong Y, Chen J, Xie Y, Wang Y, Cheng C. Toxicity and Sublethal Effects of Diamide Insecticides on Key Non-Target Natural Predators, the Larvae of Coccinella septempunctata L. (Coleoptera: Coccinellidae). TOXICS 2023; 11:270. [PMID: 36977035 PMCID: PMC10057643 DOI: 10.3390/toxics11030270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 03/13/2023] [Accepted: 03/14/2023] [Indexed: 06/18/2023]
Abstract
Coccinella septempunctata (ladybird) is an extremely important natural predator that feeds on aphids. An assessment of the toxicity of pesticides on environmental organisms is an essential component of Integrated Pest Management (IPM) strategies. This study evaluated diamide insecticides' toxicity at lethal and 30% lethal doses (LR30) against C. septempunctata larvae. The pre-imaginal median lethal doses (LR50) of chlorantraniliprole 10% SC, tetrachlorantraniliprole 10% SC, and broflanilide 10% SC were calculated to be 42.078, 289.516, and 0.0943 g active ingredient (a.i.)/ha, respectively. The mortality tests demonstrated that chlorantraniliprole and tetrachlorantraniliprole are comparatively less toxic to C. septempunctata than broflanilide, which were detected to be highly toxic to C. septempunctata. The mortality rates of the groups treated with the three diamide insecticides tended to stabilize after 96 h, extending to the pre-imaginal stage. Furthermore, when compared to broflanilide, which had a much higher potential risk, the hazard quotient (HQ) values indicated that chlorantraniliprole and tetrachlorantraniliprole have a lower risk potential for C. septempunctata in farmland and off farmland. The LR30 dose induces abnormalities in the development phase 4th-instar larvae weight, pupal weight, and adult weight of treated C. septempunctata. The study emphasizes the importance of assessing the adverse effects of diamide insecticides on natural predator species that serve as biological control agents in agricultural IPM strategies.
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Affiliation(s)
- Yunbo Cong
- School of Environmental and Chemical Engineering, Shenyang University of Technology, Shenyang 110870, China
- Key Laboratory for Chemical Pesticide of Shandong Province, Shandong Academy of Pesticide Sciences, Ji’nan 250100, China
| | - Jixiang Chen
- Key Laboratory for Chemical Pesticide of Shandong Province, Shandong Academy of Pesticide Sciences, Ji’nan 250100, China
| | - Yinping Xie
- Key Laboratory for Chemical Pesticide of Shandong Province, Shandong Academy of Pesticide Sciences, Ji’nan 250100, China
| | - Yingxiu Wang
- Key Laboratory for Chemical Pesticide of Shandong Province, Shandong Academy of Pesticide Sciences, Ji’nan 250100, China
| | - Chunsheng Cheng
- School of Environmental and Chemical Engineering, Shenyang University of Technology, Shenyang 110870, China
- Shenyang Research Institute of Chemical Industry, Shenyang 110021, China
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The potential role of environmental factors in modulating mitochondrial DNA epigenetic marks. VITAMINS AND HORMONES 2023; 122:107-145. [PMID: 36863791 DOI: 10.1016/bs.vh.2023.01.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/10/2023]
Abstract
Many studies implicate mitochondrial dysfunction in the development and progression of numerous chronic diseases. Mitochondria are responsible for most cellular energy production, and unlike other cytoplasmic organelles, mitochondria contain their own genome. Most research to date, through investigating mitochondrial DNA copy number, has focused on larger structural changes or alterations to the entire mitochondrial genome and their role in human disease. Using these methods, mitochondrial dysfunction has been linked to cancers, cardiovascular disease, and metabolic health. However, like the nuclear genome, the mitochondrial genome may experience epigenetic alterations, including DNA methylation that may partially explain some of the health effects of various exposures. Recently, there has been a movement to understand human health and disease within the context of the exposome, which aims to describe and quantify the entirety of all exposures people encounter throughout their lives. These include, among others, environmental pollutants, occupational exposures, heavy metals, and lifestyle and behavioral factors. In this chapter, we summarize the current research on mitochondria and human health, provide an overview of the current knowledge on mitochondrial epigenetics, and describe the experimental and epidemiologic studies that have investigated particular exposures and their relationships with mitochondrial epigenetic modifications. We conclude the chapter with suggestions for future directions in epidemiologic and experimental research that is needed to advance the growing field of mitochondrial epigenetics.
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Low Dose of BPA Induces Liver Injury through Oxidative Stress, Inflammation and Apoptosis in Long-Evans Lactating Rats and Its Perinatal Effect on Female PND6 Offspring. Int J Mol Sci 2023; 24:ijms24054585. [PMID: 36902016 PMCID: PMC10002922 DOI: 10.3390/ijms24054585] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 02/17/2023] [Accepted: 02/22/2023] [Indexed: 03/03/2023] Open
Abstract
Bisphenol A (BPA) is a phenolic compound used in plastics elaboration for food protection or packaging. BPA-monomers can be released into the food chain, resulting in continuous and ubiquitous low-dose human exposure. This exposure during prenatal development is especially critical and could lead to alterations in ontogeny of tissues increasing the risk of developing diseases in adulthood. The aim was to evaluate whether BPA administration (0.036 mg/kg b.w./day and 3.42 mg/kg b.w./day) to pregnant rats could induce liver injury by generating oxidative stress, inflammation and apoptosis, and whether these effects may be observed in female postnatal day-6 (PND6) offspring. Antioxidant enzymes (CAT, SOD, GR, GPx and GST), glutathione system (GSH/GSSG) and lipid-DNA damage markers (MDA, LPO, NO, 8-OHdG) were measured using colorimetric methods. Inducers of oxidative stress (HO-1d, iNOS, eNOS), inflammation (IL-1β) and apoptosis (AIF, BAX, Bcl-2 and BCL-XL) were measured by qRT-PCR and Western blotting in liver of lactating dams and offspring. Hepatic serum markers and histology were performed. Low dose of BPA caused liver injury in lactating dams and had a perinatal effect in female PND6 offspring by increasing oxidative stress levels, triggering an inflammatory response and apoptosis pathways in the organ responsible for detoxification of this endocrine disruptor.
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Morphological, immunohistochemical, and biochemical study on the ameliorative effect of gallic acid against bisphenol A-induced nephrotoxicity in male albino rats. Sci Rep 2023; 13:1732. [PMID: 36720896 PMCID: PMC9889795 DOI: 10.1038/s41598-023-28860-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 01/25/2023] [Indexed: 02/01/2023] Open
Abstract
This study aimed to determine the effect of gallic acid (GA) on ameliorating bisphenol A (BPA) nephrotoxicity in male rat kidneys. Forty rats were assigned randomly into two groups: control (ten animals) and BPA (40 mg/kg bwt) (thirty animals), the second group was divided into three subgroups: BPA alone, BPA + G50 (50 mg/kg bwt), and BPA + G200 (200 mg/kg bwt). The biochemical analysis included measurements of the contents of nitric oxide, lipid peroxidation, reactive oxygen species, and cytokines (interleukin-1α and interleukin-6) in the kidney. The antioxidant enzymes catalase and superoxide dismutase were also measured in the kidney. Kidney function was assessed by determining uric acid, urea, and creatinine levels. The morphological investigations included hematoxylin and eosin staining for assessing the general histology and determining the glomerular and corpuscular areas, the tubular cell degeneration mean area, and the mean leukocyte infiltration area. Also, collagen fiber intensity and polysaccharide content were analyzed. Furthermore, immunohistochemical, morphometric, and ultrastructural studies were carried out. The results revealed morphological, immunohistochemical, and biochemical alterations in the kidney. Most of these changes showed a satisfactory improvement of kidney damage when BPA-administered rats were treated with GA at both doses. In conclusion, GA exhibited a strong protective effect against BPA-induced nephrotoxicity.
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Hong L, Xu Y, Wang D, Zhang Q, Li X, Xie C, Wu J, Zhong C, Fu J, Geng S. Sulforaphane ameliorates bisphenol A-induced hepatic lipid accumulation by inhibiting endoplasmic reticulum stress. Sci Rep 2023; 13:1147. [PMID: 36670177 PMCID: PMC9859828 DOI: 10.1038/s41598-023-28395-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 01/18/2023] [Indexed: 01/22/2023] Open
Abstract
The aim of the present study was to investigate the role of endoplasmic reticulum (ER) stress in bisphenol A (BPA) - induced hepatic lipid accumulation as well as the protective effects of Sulforaphane (SFN) in this process. Human hepatocyte cell line (LO2) and C57/BL6J mice were used to examine BPA-triggered hepatic lipid accumulation and the underlying mechanism. Hepatic lipid accumulation, triglycerides (TGs) levels, the expression levels of lipogenesis-related genes and proteins in the ER stress pathway were measured. It was revealed that BPA treatment increased the number of lipid droplets, the levels of TG and mRNAs expression of lipogenesis-related genes, and activated the ER stress pathway. These changes were inhibited by an ER stress inhibitor 4-phenylbutyric acid. SFN treatment abrogated BPA-altered hepatic lipid metabolism and ameliorated BPA-induced ER stress-related markers. Together, these findings suggested that BPA activated ER stress to promote hepatic lipid accumulation, and that SFN reversed those BPA effects by alleviating ER stress.
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Affiliation(s)
- Lixia Hong
- Department of Nutrition and Food Safety, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China
| | - Yide Xu
- Department of Nutrition and Food Safety, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China
| | - Dongdong Wang
- Department of Nutrition and Food Safety, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China
| | - Qi Zhang
- Department of Nutrition and Food Safety, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China
| | - Xiaoting Li
- Department of Nutrition and Food Safety, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China
| | - Chunfeng Xie
- Department of Nutrition and Food Safety, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China
| | - Jieshu Wu
- Department of Nutrition and Food Safety, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China
| | - Caiyun Zhong
- Department of Nutrition and Food Safety, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China.
| | - Jinyan Fu
- Department of Nutrition, Wuxi Maternal and Child Health Care Hospital, Wuxi, 214002, Jiangsu, China.
| | - Shanshan Geng
- Department of Nutrition and Food Safety, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China.
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Chakraborty S, Dissanayake M, Godwin J, Wang X, Bhandari RK. Ancestral BPA exposure caused defects in the liver of medaka for four generations. THE SCIENCE OF THE TOTAL ENVIRONMENT 2023; 856:159067. [PMID: 36174697 PMCID: PMC10593180 DOI: 10.1016/j.scitotenv.2022.159067] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Revised: 07/01/2022] [Accepted: 09/23/2022] [Indexed: 06/16/2023]
Abstract
Environmental chemicals can induce liver defects in experimental animals due to their direct and acute exposure. It is not clear whether environmental chemical exposures result in the transgenerational passage of liver defects in subsequent generations living in an uncontaminated environment. Bisphenol A (BPA), a plasticizer chemical, has been ubiquitous in the environment in the recent decade. Every organism is exposed to this chemical at some point during its lifetime. Literature suggests that direct BPA exposure can result in several metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). Despite the phasing out of BPA from several consumer goods, it is unclear whether ancestral BPA exposure causes liver health problems in the unexposed future generations. Here, we demonstrate an advanced stage of NAFLD in the grandchildren (F2 generation) of medaka fish (Oryzias latipes) due to embryonic BPA exposure in the grandparental generation (F0), which persists for five generations (F4) even in the absence of BPA. The severity of transgenerational NAFLD phenotype included steatosis together with perisinusoidal fibrosis and apoptosis of hepatocytes. Adult females developed more severe histopathological conditions in the liver than males. Genes encoding enzymes involved in lipolytic pathways were significantly decreased. The present results suggest that ancestral BPA exposure can result in transgenerational metabolic diseases that can persist for five generations and that the NAFLD trait is sexually dimorphic. Given that ancestral BPA exposure can lead to altered metabolic health outcomes in the subsequent unexposed generations, the development of the methods and strategies to mitigate the transgenerational onset of metabolic diseases seem imperative to protect future generations.
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Affiliation(s)
- Sourav Chakraborty
- Department of Biology, University of North Carolina Greensboro, Greensboro, NC 27412, USA
| | - Manthi Dissanayake
- Department of Biology, University of North Carolina Greensboro, Greensboro, NC 27412, USA
| | - Julia Godwin
- Department of Biology, University of North Carolina Greensboro, Greensboro, NC 27412, USA
| | - Xuegeng Wang
- Department of Biology, University of North Carolina Greensboro, Greensboro, NC 27412, USA; Institute of Modern Aquaculture Science and Engineering, College of Life Sciences, South China Normal University, Guangzhou 510631, PR China
| | - Ramji Kumar Bhandari
- Department of Biology, University of North Carolina Greensboro, Greensboro, NC 27412, USA.
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Amin MAS, Sonpol HMA, Gouda RHE, Aboregela AM. Bisphenol A enhances apoptosis, fibrosis, and biochemical fluctuations in the liver of adult male rats with possible regression after recovery. Anat Rec (Hoboken) 2023; 306:213-225. [PMID: 35773941 DOI: 10.1002/ar.25032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 06/12/2022] [Accepted: 06/17/2022] [Indexed: 01/29/2023]
Abstract
Bisphenol A (BPA) is an environmental contaminant that might be harmful. Human exposure to BPA can occur during the fetal and postnatal periods and extends throughout life. This study aimed to estimate the effects of oral administration of BPA on rat liver and assess the possibility of recovery after cessation. Adult male albino rats were orally administered with BPA (50 mg/kg body weight) for 8 weeks, and then one group was left to recover for 4 weeks. Histological, immunohistochemical, biochemical, and quantitative real-time polymerase chain reaction assessments were performed. Loss of hepatic architecture, vascular dilatation congestion, and exudation, as well as cellular vacuolation, fat accumulation, and pyknotic nuclei were detected. Furthermore, inflammatory infiltration, localized metaplasia, and excessive collagen deposition in the portal triad were observed. Expression of Bcl-2-associated X protein and transforming growth factor beta 1 was prominent, denoting apoptosis and fibrosis. After the administration of BPA, serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, cholesterol, triglycerides, and low-density lipoproteins were enhanced. Additionally, total protein, albumin, and high-density lipoproteins decreased. After a recovery for 4 weeks, hepatic cellular and vascular pathologies returned to normal, except for some inflammatory infiltration. Regarding biochemical affection, most of the parameters were directed toward normal during recovery. However, most of them were still significantly different from controls. This explored BPA hepatotoxicity from structural and functional aspects, and the possible spontaneous reversibility was confirmed. However, the precise mechanisms underlying hepatotoxicity or recovery need more in-depth investigations.
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Affiliation(s)
| | - Hany M A Sonpol
- Human Anatomy and Embryology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.,Basic Medical Sciences Department, College of Medicine, University of Bisha, Bisha, Kingdom of Saudi Arabia
| | - Rehab Hassan Elbanna Gouda
- Medical Biochemistry Unit, Zagazig Scientific and Medical Research Center, Zagazig University, Zagazig, Egypt
| | - Adel Mohamed Aboregela
- Human Anatomy and Embryology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.,Basic Medical Sciences Department, College of Medicine, University of Bisha, Bisha, Kingdom of Saudi Arabia
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26
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Majid M, Farhan A, Baig MW, Khan MT, Kamal Y, Hassan SSU, Bungau S, Haq IU. Ameliorative Effect of Structurally Divergent Oleanane Triterpenoid, 3-Epifriedelinol from Ipomoea batatas against BPA-Induced Gonadotoxicity by Targeting PARP and NF-κB Signaling in Rats. Molecules 2022; 28:molecules28010290. [PMID: 36615482 PMCID: PMC9822353 DOI: 10.3390/molecules28010290] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 12/19/2022] [Accepted: 12/24/2022] [Indexed: 12/31/2022] Open
Abstract
The pentacyclic triterpenoids (PTs) of plant origin are reputed to restrain prostate cancer (PCa) cell proliferation. This study aims to assess 3-epifriedelinol (EFD) isolated from aerial part of Ipomoea batatas against PCa and its potential mechanism, in vitro and in vivo. Molecular docking affirms good binding affinity of the compound with target proteins exhibiting binding energy of −7.9 Kcal/mol with BAX, −8.1 Kcal/mol (BCL-2), −1.9 Kcal/mol (NF-κB) and −8.5 Kcal/mol with P53. In the MTT assay, EFD treatment (3−50 µM) showed a significant (p < 0.05 and p < 0.01) dose and time dependent drop in the proliferative graph of DU145 and PC3, and an upsurge in apoptotic cell population. EFD displayed substantial IC50 against DU145 (32.32 ± 3.72 µM) and PC3 (35.22 ± 3.47 µM). According to Western blots, EFD administration significantly enhanced the cleavage of caspases and PARP, elevated BAX and P53 and decreased BCL-2 and NF-κB expression, thereby triggering apoptosis in PCa cells. When male Sprague Dawley rats were intoxicated with Bisphenol A (BPA), an apparent increase in prostate mass (0.478 ± 0.08 g) in comparison to control (0.385 ± 0.03 g) indicates prostatitis. Multidose treatment of EFD (10 mg/kg) significantly reduced prostate size (0.404 ± 0.05 g). EFD exhibited substantial curative potential in vivo, as hematological, hormonal and histopathological parameters have been significantly improved. Reduced peroxidation (TBARS), and suppression of inflammatory markers i.e., NO, IL-6 and TNF-α, signposts substantial antiinflammatory potential of the compound. Overall, EFD has shown better binding affinity with target molecules, acceptable ADMET profile, potent antiproliferative and apoptotic nature and significant reduction in inflamed prostate mass of rats. The present study demonstrates acceptable physicochemical and pharmacokinetic properties of the compound with excellent drugable nature, hence EFD in the form of standardized formulation can be developed as primary or adjuvant therapy against PCa and toxins-induced gonadotoxicity.
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Affiliation(s)
- Muhammad Majid
- Faculty of Pharmacy, Hamdard University, Islamabad 45550, Pakistan
| | - Anam Farhan
- Department of Biology, School of Science and Engineering, Lahore University of Management Sciences, Lahore 54792, Pakistan
| | - Muhammad Waleed Baig
- Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Muhammad Tariq Khan
- Faculty of Pharmacy, Capital University of Science and Technology, Islamabad 44000, Pakistan
| | - Yousaf Kamal
- Faculty of Pharmacy, Hamdard University, Islamabad 45550, Pakistan
| | - Syed Shams ul Hassan
- Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
- Correspondence: (S.S.u.H.); (S.B.); (I.-u.H.)
| | - Simona Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania
- Correspondence: (S.S.u.H.); (S.B.); (I.-u.H.)
| | - Ihsan-ul Haq
- Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan
- Correspondence: (S.S.u.H.); (S.B.); (I.-u.H.)
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Potential Effects of Bisphenol A on the Heart and Coronary Artery of Adult Male Rats and the Possible Role of L-Carnitine. J Toxicol 2022; 2022:7760594. [PMID: 36601412 PMCID: PMC9807306 DOI: 10.1155/2022/7760594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 12/07/2022] [Accepted: 12/19/2022] [Indexed: 12/28/2022] Open
Abstract
Bisphenol A (BPA) is an environmental toxin utilized for the production of polycarbonate plastics and epoxy resins. Due to BPA's extensive production and environmental contamination, human exposure is unavoidable. The effects of low-dose of BPA on various body tissues and organs remain controversial. Our study investigated the potential of BPA to induce biochemical, histopathological, and immunohistochemical changes in the coronary artery and myocardium and the potential protective role of L-carnitine (LC). 24 adult Wistar albino male rats were divided equally into a control group, a BPA-treated group (40 mg/kg/d, by gavage for 4 weeks), and a BPA plus LC-treated group (received 40 mg/kg/d of BPA and 300 mg/kg/d of LC, by gavage for 4 weeks). BPA-exposed rats demonstrated structural anomalies in the coronary artery tissue including vacuolation of cells in the media and detachment of the endothelium of the intima. Congestion of blood vessels and infiltration by polynuclear cells were observed in the myocardium. There was an enhanced collagen deposition in both tissues indicating fibrosis. Immunohistochemical changes included enhanced eNOS and caspase-3 expression in the coronary artery and myocardium indicating vascular disease and apoptosis, respectively. Oxidative damage was evident in the coronary artery and the myocardium of BPA-treated rats, which was indicated by the reduced level of glutathione (GSH) and elevated malondydehyde (MDA) levels. The coadministration of LC significantly improved BPA-induced structural alterations and oxidative stress. In conclusion, BPA could potentially cause pathologic changes and oxidative damage in the coronary artery and myocardium, which could be improved by LC coadministration.
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Sharma P, Vishwakarma R, Varjani S, Gautam K, Gaur VK, Farooqui A, Sindhu R, Binod P, Awasthi MK, Chaturvedi P, Pandey A. Multi-omics approaches for remediation of bisphenol A: Toxicity, risk analysis, road blocks and research perspectives. ENVIRONMENTAL RESEARCH 2022; 215:114198. [PMID: 36063912 DOI: 10.1016/j.envres.2022.114198] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 05/01/2022] [Accepted: 08/20/2022] [Indexed: 06/15/2023]
Abstract
In this "plastic era" with the increased use of plastic in day today's life the accumulation of its degraded products like microplastics or plastic additives such as Bisphenol A(BPA) is also increasing. BPA is an endocrine-disrupting chemical used as a plasticizing agent in clear plastic, building materials, coatings, and epoxy resin. Several enzymes including laccases and lipases have been studied for the reduction of BPA toxicity. Over the decades of encountering these toxicants, microorganisms have evolved to degrade different classes of plastic additives. Since the degradation of BPA is a long process thus meta-omics approaches have been employed to identify the active microbiota and microbial dynamics involved in the mitigation of BPA. It is also necessary to investigate the impact of processing activities on transit of BPA in food items and to limit its entrance in food world. This review summarizes a comprehensive overview on BPA sources, toxicity, bio-based mitigation approaches along with a deeper understanding of multi-omics approaches for its reduction and risk analysis. Knowledge gaps and opportunities have been comprehensively compiled that would aid the state-of-the-art information in the available literature for the researchers to further address this issue.
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Affiliation(s)
- Poonam Sharma
- Department of Bioengineering, Integral University, Lucknow, 226 026, India
| | - Reena Vishwakarma
- Department of Bioengineering, Integral University, Lucknow, 226 026, India
| | - Sunita Varjani
- Gujarat Pollution Control Board, Gandhinagar, 382 010, India.
| | - Krishna Gautam
- Centre of Energy and Environmental Sustainability, Lucknow, 226 021, India
| | - Vivek K Gaur
- Centre of Energy and Environmental Sustainability, Lucknow, 226 021, India; School of Energy and Chemical Engineering, UNIST, Ulsan, 44919, Republic of Korea
| | - Alvina Farooqui
- Department of Bioengineering, Integral University, Lucknow, 226 026, India
| | - Raveendran Sindhu
- Department of Food Technology, T K M Institute of Technology, Kollam, 691 505, Kerala, India
| | - Parameswaran Binod
- CSIR-National Institute for Interdisciplinary Science and Technology (NIIST), Trivandrum, 695 019, Kerala, India
| | - Mukesh Kumar Awasthi
- College of Natural Resources and Environment, Northwest A& F University, Yangling, Shaanxi Province, 712100, PR China
| | - Preeti Chaturvedi
- Aquatic Toxicology Laboratory, Environmental Toxicology Group, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, M.G. Marg, Lucknow, 226001, Uttar Pradesh, India
| | - Ashok Pandey
- Centre of Energy and Environmental Sustainability, Lucknow, 226 021, India; Centre for Innovation and Translational Research, CSIR-Indian Institute of Toxicology Research, Lucknow, 226 001, India; Sustainability Cluster, School of Engineering, University of Petroleum and Energy Studies, Dehradun, 248 007, India
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29
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Nayak D, Adiga D, Khan NG, Rai PS, Dsouza HS, Chakrabarty S, Gassman NR, Kabekkodu SP. Impact of Bisphenol A on Structure and Function of Mitochondria: A Critical Review. REVIEWS OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY 2022; 260:10. [DOI: 10.1007/s44169-022-00011-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 10/26/2022] [Indexed: 04/02/2024]
Abstract
AbstractBisphenol A (BPA) is an industrial chemical used extensively to manufacture polycarbonate plastics and epoxy resins. Because of its estrogen-mimicking properties, BPA acts as an endocrine-disrupting chemical. It has gained attention due to its high chances of daily and constant human exposure, bioaccumulation, and the ability to cause cellular toxicities and diseases at extremely low doses. Several elegant studies have shown that BPA can exert cellular toxicities by interfering with the structure and function of mitochondria, leading to mitochondrial dysfunction. Exposure to BPA results in oxidative stress and alterations in mitochondrial DNA (mtDNA), mitochondrial biogenesis, bioenergetics, mitochondrial membrane potential (MMP) decline, mitophagy, and apoptosis. Accumulation of reactive oxygen species (ROS) in conjunction with oxidative damage may be responsible for causing BPA-mediated cellular toxicity. Thus, several reports have suggested using antioxidant treatment to mitigate the toxicological effects of BPA. The present literature review emphasizes the adverse effects of BPA on mitochondria, with a comprehensive note on the molecular aspects of the structural and functional alterations in mitochondria in response to BPA exposure. The review also confers the possible approaches to alleviate BPA-mediated oxidative damage and the existing knowledge gaps in this emerging area of research.
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Alvi M, Rehman K, Akash MSH, Yaqoob A, Shoaib SM. Determination of Metabolomics Profiling in BPA-Induced Impaired Metabolism. Pharmaceutics 2022; 14:pharmaceutics14112496. [PMID: 36432690 PMCID: PMC9692868 DOI: 10.3390/pharmaceutics14112496] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 11/14/2022] [Accepted: 11/16/2022] [Indexed: 11/19/2022] Open
Abstract
Exposure to bisphenol A (BPA) is unavoidable and it has far-reaching negative effects on living systems. This study aimed to explore the toxic effects of BPA in an experimental animal model through a metabolomics approach that is useful in measuring small molecule perturbations. Beside this, we also examined the ameliorative effects of resveratrol (RSV) against BPA-induced disturbances in experimental mice. This study was conducted for 28 days, and the results showed that BPA indeed induced an impairment in amino acid metabolism, taking place in the mitochondria by significantly (p < 0.05) decreasing the levels of certain amino acids, i.e., taurine, threonine, asparagine, leucine, norleucine, and glutamic acid in the mice plasma. However, the administration of RSV did prove effective against the BPA-induced intoxication and significantly (p < 0.05) restored the level of free amino acids. Lipid metabolites, L-carnitine, sphinganine, phytosphingosine, and lysophosphatidylcholine were also determined in the mice serum. A significant (p < 0.05) decline in glutathione peroxidase (GPx), superoxide dismutase (SOD,) glutathione, and catalase levels and an elevation in malondialdehyde level in the BPA group confirmed the generation of oxidative stress and lipid peroxidation in experimental mice exposed to BPA. The expression of Carnitine palmitoyltransferase I (CPT-I), carnitine palmitoyltransferase II (CPT-II), lecithin−cholesterol acyltransferase (LCAT), carnitine O-octanoyltransferase (CROT), carnitine-acylcarnitine translocase (CACT), and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) genes was significantly upregulated in the liver tissue homogenates of experimental mice exposed to BPA, although RSV regulated the expression of these genes when compared with BPA treated experimental mice. CPT-I, CPT-II, and CACT genes are located in the mitochondria and are involved in the metabolism and transportation of carnitine. Hence, this study confirms that BPA exposure induced oxidative stress, upregulated gene expression, and impaired lipid and amino acid metabolism in experimental mice.
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Affiliation(s)
- Maria Alvi
- Department of Pharmaceutical Chemistry, Government College University, Faisalabad 38000, Pakistan
| | - Kanwal Rehman
- Department of Pharmacy, The Women University, Multan 66000, Pakistan
| | - Muhammad Sajid Hamid Akash
- Department of Pharmaceutical Chemistry, Government College University, Faisalabad 38000, Pakistan
- Correspondence:
| | - Azka Yaqoob
- Department of Pharmaceutical Chemistry, Government College University, Faisalabad 38000, Pakistan
| | - Syed Muhammad Shoaib
- Drugs Testing Laboratory, Faisalabad, Primary & Secondary Healthcare Department, Government of the Punjab, Lahore 54000, Pakistan
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31
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Arulanandam CD, Hwang JS, Rathinam AJ, Dahms HU. Evaluating different web applications to assess the toxicity of plasticizers. Sci Rep 2022; 12:19684. [PMID: 36385271 PMCID: PMC9668977 DOI: 10.1038/s41598-022-18327-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 08/09/2022] [Indexed: 11/18/2022] Open
Abstract
Plasticizers increase the flexibility of plastics. As environmental leachates they lead to increased water and soil pollution, as well as to serious harm to human health. This study was set out to explore various web applications to predict the toxicological properties of plasticizers. Web-based tools (e.g., BOILED-Egg, LAZAR, PROTOX-II, CarcinoPred-EL) and VEGA were accessed via an 5th-10th generation computer in order to obtain toxicological predictions. Based on the LAZAR mutagenicity assessment was only bisphenol F predicted as mutagenic. The BBP and DBP in RF; DEHP in RF and XGBoost; DNOP in RF and XGBoost models were predicted as carcinogenic in the CarcinoPred-EL web application. From the bee predictive model (KNN/IRFMN) BPF, di-n-propyl phthalate, diallyl phthalate, dibutyl phthalate, and diisohexyl phthalate were predicted as strong bee toxicants. Acute toxicity for fish using the model Sarpy/IRFMN predicted 19 plasticizers as strong toxicants with LC50 values of less than 1 mg/L. This study also considered plasticizer effects on gastrointestinal absorption and other toxicological endpoints.
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Affiliation(s)
- Charli Deepak Arulanandam
- grid.412019.f0000 0000 9476 5696Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, 80708 Taiwan, ROC ,grid.412019.f0000 0000 9476 5696Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, 80708 Taiwan, ROC
| | - Jiang-Shiou Hwang
- grid.260664.00000 0001 0313 3026Institute of Marine Biology, National Taiwan Ocean University, Keelung, 20224 Taiwan, ROC ,grid.260664.00000 0001 0313 3026Center of Excellence for Ocean Engineering, National Taiwan Ocean University, Keelung, 20224 Taiwan, ROC ,grid.260664.00000 0001 0313 3026Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung, 20224 Taiwan, ROC
| | - Arthur James Rathinam
- grid.411678.d0000 0001 0941 7660Department of Marine Science, Bharathidasan University, Tiruchirappalli, 620 024, India
| | - Hans-Uwe Dahms
- grid.412019.f0000 0000 9476 5696Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, 80708 Taiwan, ROC ,grid.412019.f0000 0000 9476 5696Research Center of Precision Environmental Medicine, Kaohsiung Medical University, Kaohsiung, 807 Taiwan ,grid.412036.20000 0004 0531 9758Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, No. 70, Lienhai Road, Kaohsiung, 80424 Taiwan, ROC
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Manzoor MF, Tariq T, Fatima B, Sahar A, Tariq F, Munir S, Khan S, Nawaz Ranjha MMA, Sameen A, Zeng XA, Ibrahim SA. An insight into bisphenol A, food exposure and its adverse effects on health: A review. Front Nutr 2022; 9:1047827. [PMID: 36407508 PMCID: PMC9671506 DOI: 10.3389/fnut.2022.1047827] [Citation(s) in RCA: 61] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Accepted: 10/12/2022] [Indexed: 08/13/2023] Open
Abstract
Bisphenol A (BPA) is a synthetic chemical widely employed to synthesize epoxy resins, polymer materials, and polycarbonate plastics. BPA is abundant in the environment, i.e., in food containers, water bottles, thermal papers, toys, medical devices, etc., and is incorporated into soil/water through leaching. Being a potent endocrine disrupter, and has the potential to alter several body mechanisms. Studies confirmed its anti-androgen action and estrogen-like effects, which impart many negative health impacts, especially on the immune system, neuroendocrine process, and reproductive mechanism. Moreover, it can also induce mutagenesis and carcinogenesis, as per recent scientific research. This review focuses on BPA's presence and concentrations in different environments, food sources and the basic mechanisms of BPA-induced toxicity and health disruptions. It is a unique review of its type because it focuses on the association of cancer, hormonal disruption, immunosuppression, and infertility with BPA. These issues are widespread today, and BPA significantly contributes to their incidence because of its wide usage in daily life utensils and other accessories. The review also discusses researched-based measures to cope with the toxic chemical.
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Affiliation(s)
- Muhammad Faisal Manzoor
- Guangdong Provincial Key Laboratory of Intelligent Food Manufacturing, Foshan University, Foshan, China
- School of Food Science and Engineering, South China University of Technology, Guangzhou, China
| | - Tayyaba Tariq
- National Institute of Food Science and Technology, University of Agriculture, Faisalabad, Punjab, Pakistan
| | - Birjees Fatima
- National Institute of Food Science and Technology, University of Agriculture, Faisalabad, Punjab, Pakistan
| | - Amna Sahar
- Department of Food Engineering, University of Agriculture, Faisalabad, Punjab, Pakistan
| | - Farwa Tariq
- National Institute of Food Science and Technology, University of Agriculture, Faisalabad, Punjab, Pakistan
| | - Seemal Munir
- National Institute of Food Science and Technology, University of Agriculture, Faisalabad, Punjab, Pakistan
| | - Sipper Khan
- School of Food and Agricultural Sciences, University of Management and Technology, Lahore, Pakistan
| | | | - Aysha Sameen
- Department of Food Science and Technology, Government College Women University Faisalabad, Faisalabad, Pakistan
| | - Xin-An Zeng
- Guangdong Provincial Key Laboratory of Intelligent Food Manufacturing, Foshan University, Foshan, China
- School of Food Science and Engineering, South China University of Technology, Guangzhou, China
| | - Salam A. Ibrahim
- Food Microbiology and Biotechnology Laboratory, North Carolina Agricultural and Technical State University, Greensboro, NC, United States
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Molina-López AM, Bujalance-Reyes F, Urbano MT, Lora-Benítez A, Ayala-Soldado N, Moyano-Salvago R. Analysis of Blood Biochemistry and Pituitary-Gonadal Histology after Chronic Exposure to Bisphenol-A of Mice. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph192113894. [PMID: 36360773 PMCID: PMC9659152 DOI: 10.3390/ijerph192113894] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 10/21/2022] [Accepted: 10/22/2022] [Indexed: 05/12/2023]
Abstract
Bisphenol-A is an emerging pollutant that is widespread in the environment, and to which live beings are continuously and inadvertently exposed. It is a substance with an endocrine-disrupting capacity, causing alterations in the reproductive, immunological, and neurological systems, among others, as well as metabolic alterations. Our study aimed to assess its clinical signs, and effects on the most relevant blood biochemical parameters, and to evaluate pituitary and gonadal histology after a chronic exposure of adult mice to different BPA doses (0.5, 2, 4, 50 and 100 µg/kg BW/day) through their drinking water. The biochemical results showed that a marked significant reduction (p < 0.05) was produced in the levels of serum glucose, hypoproteinaemia and hypoalbuminemia in the groups exposed to the highest doses, whereas in the group exposed to 50 µg/kg BW/day the glucose and total protein levels dropped, and the animals exposed to 100 µg/kg BW/day experienced a diminution in albumin levels. In the case of the group exposed to 50 µg/kg BW/day, however, hypertriglyceridemia and hypercholesterolemia were determined, and the blood parameters indicating kidney alterations such as urea and creatinine experienced a significant increase (p < 0.05) with respect to the controls. Regarding the pituitary and gonads, none of the animals exposed presented histological alterations at the doses tested, giving similar images to those of the control group. These results suggest that continuous exposure to low BPA doses could trigger an inhibition of hepatic gluconeogenesis, which would result in a hypoglycaemic state, together with an induction of the enzymes responsible for lipidic synthesis, a mechanism by which the increase in the lipid and serum cholesterol levels could be explained. Likewise, the decline in the protein and albumin levels would be indicative of a possible hepatic alteration, and the increase in urea and creatinine would point to a possible renal perturbation, derived from continuous exposure to this xenobiotic. Based on our results, it could be said that chronic exposure to low BPA doses would not produce any clinical signs or histological pituitary-gonadal effects, but it could cause modifications in some blood biochemical parameters, that could initially indicate a possible hepatic and renal effect.
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Affiliation(s)
- Ana M. Molina-López
- Departamento Anatomía y Anatomía Patológica Comparadas y Toxicología, Unidad de Investigación Competitiva Zoonosis y Enfermedades Emergentes Desde la Perspectiva de Una Salud ENZOEM, Campus de Rabanales, Universidad de Córdoba, Edificio Darwin, 14071 Córdoba, Spain
- Correspondence: (A.M.M.-L.); (A.L.-B.)
| | - Francisca Bujalance-Reyes
- Departamento Anatomía y Anatomía Patológica Comparadas y Toxicología, Campus de Rabanales, Universidad de Córdoba, Edificio Darwin, 14071 Córdoba, Spain
| | - María Teresa Urbano
- Departamento Anatomía y Anatomía Patológica Comparadas y Toxicología, Campus de Rabanales, Universidad de Córdoba, Edificio Darwin, 14071 Córdoba, Spain
| | - Antonio Lora-Benítez
- Departamento Anatomía y Anatomía Patológica Comparadas y Toxicología, Campus de Rabanales, Universidad de Córdoba, Edificio Darwin, 14071 Córdoba, Spain
- Correspondence: (A.M.M.-L.); (A.L.-B.)
| | - Nahúm Ayala-Soldado
- Departamento Anatomía y Anatomía Patológica Comparadas y Toxicología, Campus de Rabanales, Universidad de Córdoba, Edificio Darwin, 14071 Córdoba, Spain
| | - Rosario Moyano-Salvago
- Departamento Anatomía y Anatomía Patológica Comparadas y Toxicología, Unidad de Investigación Competitiva Zoonosis y Enfermedades Emergentes Desde la Perspectiva de Una Salud ENZOEM, Campus de Rabanales, Universidad de Córdoba, Edificio Darwin, 14071 Córdoba, Spain
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Abd-Elnaby YA, ElSayed IE, AbdEldaim MA, Badr EA, Abdelhafez MM, Elmadbouh I. Anti-inflammatory and antioxidant effect of Moringa oleifera against bisphenol-A-induced hepatotoxicity. EGYPTIAN LIVER JOURNAL 2022. [DOI: 10.1186/s43066-022-00219-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Non-pharmacological exposure or pharmacological drug-induced hepatic injury is the most common cause of hepatotoxicity. This study was conducted to evaluate the effect of Moringa oleifera leaf extract against bisphenol-A (BPA)-induced hepatic toxicity in rats.
Methods
Rats (n=56) were randomized into 7 groups (8 rats/each). Control groups: rats received olive oil or Moringa oleifera (400mg/kg) orally for 42 days. Hepatotoxicity groups: rats received BPA (50mg/kg BW) orally in a 1-ml olive oil for 42 days. Reversal groups: rats received Moringa oleifera (200 or 400mg/kg) and BPA (50mg/kg BW) for 42 days. Preventive groups: rats received Moringa oleifera (200 or 400mg/kg) for 30 days followed by BPA (50mg/kg BW) for 14 days. At the end of the experiments, blood samples were collected for glucose and liver function assay, while the liver tissue samples were collected and homogenated for measuring the inflammatory/oxidant and antioxidant markers.
Results
Rats with BPA-induced hepatotoxicity have significantly increased serum aspartate transaminase (AST), alanine transaminase (ALT), and glucose; liver lysate malondialdehyde (MDA); tumor necrosis factor (TNF-α); and macrophage migrating inhibitory factor (MIF) but significantly decreased levels of liver lysate reduced glutathione (GSH) and total antioxidant capacity (TAC) levels. The administration of Moringa oleifera (especially 400mg/kg BW) in both reversal and preventive groups ameliorate the toxic effects of BPA in rats, as it decreased the activities of AST, ALT, glucose, MDA, TNF-α, and MIF levels and increased the antioxidant levels of GSH and TAC.
Conclusion
Moringa oleifera has hepatoprotective effects against BPA-induced liver damage through the regulation of antioxidants and inflammatory biomarkers.
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Adverse Effects of Bisphenol A on the Liver and Its Underlying Mechanisms: Evidence from In Vivo and In Vitro Studies. BIOMED RESEARCH INTERNATIONAL 2022; 2022:8227314. [PMID: 36017387 PMCID: PMC9398799 DOI: 10.1155/2022/8227314] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 07/06/2022] [Accepted: 07/28/2022] [Indexed: 11/17/2022]
Abstract
BPA is a known endocrine-disrupting agent that is capable of binding to the estrogen receptor and has exhibited adverse effects in many laboratory animal and in vitro studies. Moreover, it also been shown to have estrogenic, antiandrogenic, inflammatory, and oxidative properties. The widespread presence of BPA in the environment presents a considerable threat to humans. BPA has been shown to be leached into the human ecosystem, where it is commonly found in food products consumed by humans. Although the concentration is relatively low, its prolonged consumption may cause a variety of deleterious health effects. The liver is an important organ for metabolizing and detoxifying toxic metabolites to protect organisms from potentially toxic chemical insults. BPA that is ingested will be eliminated by the liver. However, it has also induced hepatoxicity and injury via various mechanisms. To find research demonstrating the effects of BPA on kidney, a number of databases, including Google Scholar, MEDLINE, PubMed, and the Directory of Open Access Journals, were searched. Thus, this review summarizes the research on the relationship between BPA and its effects on the liver-derived from animals and cellular studies. The underlying mechanism of liver injury caused by BPA is also elucidated.
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Ďurovcová I, Kyzek S, Fabová J, Makuková J, Gálová E, Ševčovičová A. Genotoxic potential of bisphenol A: A review. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2022; 306:119346. [PMID: 35489531 DOI: 10.1016/j.envpol.2022.119346] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 04/05/2022] [Accepted: 04/20/2022] [Indexed: 05/25/2023]
Abstract
Bisphenol A (BPA), as a major component of some plastic products, is abundant environmental pollutant. Due to its ability to bind to several types of estrogen receptors, it can trigger multiple cellular responses, which can contribute to various manifestations at the organism level. The most studied effect of BPA is endocrine disruption, but recently its prooxidative potential has been confirmed. BPA ability to induce oxidative stress through increased ROS production, altered activity of antioxidant enzymes, or accumulation of oxidation products of biomacromolecules is observed in a wide range of organisms - estrogen receptor-positive and -negative. Subsequently, increased intracellular oxidation can lead to DNA damage induction, represented by oxidative damage, single- and double-strand DNA breaks. Importantly, BPA shows several mechanisms of action and can trigger adverse effects on all organisms inhabiting a wide variety of ecosystem types. Therefore, the main aim of this review is to summarize the genotoxic effects of BPA on organisms across all taxa.
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Affiliation(s)
- Ivana Ďurovcová
- Department of Genetics, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovičova 6, 842 15, Bratislava, Slovakia.
| | - Stanislav Kyzek
- Department of Genetics, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovičova 6, 842 15, Bratislava, Slovakia.
| | - Jana Fabová
- Department of Genetics, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovičova 6, 842 15, Bratislava, Slovakia.
| | - Jana Makuková
- Department of Genetics, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovičova 6, 842 15, Bratislava, Slovakia.
| | - Eliška Gálová
- Department of Genetics, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovičova 6, 842 15, Bratislava, Slovakia.
| | - Andrea Ševčovičová
- Department of Genetics, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovičova 6, 842 15, Bratislava, Slovakia.
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Thabet NM, Abdel-Rafei MK, Moustafa EM. Boswellic acid protects against Bisphenol-A and gamma radiation induced hepatic steatosis and cardiac remodelling in rats: role of hepatic PPAR-α/P38 and cardiac Calcineurin-A/NFATc1/P38 pathways. Arch Physiol Biochem 2022; 128:767-785. [PMID: 32057248 DOI: 10.1080/13813455.2020.1727526] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Bisphenol-A (BPA) and gamma-radiation are two risky environmental pollutants that human beings are exposed to in everyday life and consequently they threaten human health via inducing oxidative stress, inflammation, and eventually tissue damage. This study aims at appraising the protective effect of Boswellic Acid (BA) (250 mg/kg/day, orally) administration on BPA (150 mg/kg/day, i.p) and γ-irradiation (IR) (3 Gy/week for 4 weeks up to cumulative dose of 12 Gy/experimental course) for 4 weeks-induced damage to liver and heart tissues of rats. The present results indicated a significant improvement against damage induced by BPA and IR revealed in biochemical investigations (hepatic PPAR-α/P38 and cardiac ET-1/Calcineurin-A/NFATc1/P38) and histopathological examination of liver and heart. It could be concluded that BA possesses a protective effect against these two deleterious environmental pollutants which attracted major global concerns due to their serious toxicological impact on human health.
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Affiliation(s)
- Noura M Thabet
- Radiation Biology Department National Centre for Radiation Research and Technology (NCRRT), Atomic Energy Authority, Cairo, Egypt
| | - Mohamed K Abdel-Rafei
- Radiation Biology Department National Centre for Radiation Research and Technology (NCRRT), Atomic Energy Authority, Cairo, Egypt
| | - Enas M Moustafa
- Radiation Biology Department National Centre for Radiation Research and Technology (NCRRT), Atomic Energy Authority, Cairo, Egypt
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Are BPA Substitutes as Obesogenic as BPA? Int J Mol Sci 2022; 23:ijms23084238. [PMID: 35457054 PMCID: PMC9031831 DOI: 10.3390/ijms23084238] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 03/31/2022] [Accepted: 04/05/2022] [Indexed: 02/04/2023] Open
Abstract
Metabolic diseases, such as obesity, Type II diabetes and hepatic steatosis, are a significant public health concern affecting more than half a billion people worldwide. The prevalence of these diseases is constantly increasing in developed countries, affecting all age groups. The pathogenesis of metabolic diseases is complex and multifactorial. Inducer factors can either be genetic or linked to a sedentary lifestyle and/or consumption of high-fat and sugar diets. In 2002, a new concept of “environmental obesogens” emerged, suggesting that environmental chemicals could play an active role in the etiology of obesity. Bisphenol A (BPA), a xenoestrogen widely used in the plastic food packaging industry has been shown to affect many physiological functions and has been linked to reproductive, endocrine and metabolic disorders and cancer. Therefore, the widespread use of BPA during the last 30 years could have contributed to the increased incidence of metabolic diseases. BPA was banned in baby bottles in Canada in 2008 and in all food-oriented packaging in France from 1 January 2015. Since the BPA ban, substitutes with a similar structure and properties have been used by industrials even though their toxic potential is unknown. Bisphenol S has mainly replaced BPA in consumer products as reflected by the almost ubiquitous human exposure to this contaminant. This review focuses on the metabolic effects and targets of BPA and recent data, which suggest comparable effects of the structural analogs used as substitutes.
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Molecular dissection of cellular response of pancreatic islet cells to Bisphenol-A (BPA): a comprehensive review. Biochem Pharmacol 2022; 201:115068. [DOI: 10.1016/j.bcp.2022.115068] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 04/11/2022] [Accepted: 04/25/2022] [Indexed: 12/15/2022]
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Jain R, Jain A, Jain S, Thakur SS, Jain SK. Linking bisphenol potential with deleterious effect on immune system: a review. THE NUCLEUS 2022. [DOI: 10.1007/s13237-022-00383-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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Dökmeci AH, Karaboğa İ, Güzel S, Erboğa ZF, Yılmaz A. Toxicological assessment of low-dose bisphenol A, lead and endosulfan combination: chronic toxicity study in male rats. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:10558-10574. [PMID: 34523106 DOI: 10.1007/s11356-021-16407-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 09/04/2021] [Indexed: 05/26/2023]
Abstract
In the present study, toxic effects, both alone and combined, of bisphenol A (BPA), lead (Pb) and endosulfan (ES) in the low doses were investigated in rat liver and kidney functions. In the study, bisphenol A (BPA), lead (Pb) and endosulfan (ES) were chosen because although they are the chemicals people are most frequently exposed to, no combined toxic effect studies were conducted with these chemicals. Sixty-four male Wistar albino rats were used in the study, and they were randomly divided into eight groups (n = 8 per group); control, BPA (5 mg/kg), Pb (100 ppm), ES (0.61 mg/kg), BPA+Pb, BPA+ES, Pb+ES and BPA+P+ES. The rats were sacrificed after 65 days of treatment. Severe histopathological changes in the liver and kidney tissues were observed in the rats exposed to BPA+Pb+ES combination. Elevated malondialdehyde (MDA) in the liver and decreased superoxide dismutase activity (SOD) in the kidney tissue were detected in the BPA+Pb+ES group compared to those of the control group. It was found that serum alanine aminotransferase (ALT) and blood urea nitrogen (BUN) and creatinine (CREA) levels were higher in the BPA+Pb+ES combination group than the control group. Also, combined exposure of BPA, Pb and ES caused apoptotic cell numbers and inducible nitric oxide (iNOS) to increase in the liver and kidney tissues. The results of the present study suggested that the BPA, Pb and ES caused more dramatic changes to both histological architecture and cell apoptosis in the liver and kidney tissues when there was a combined exposure.
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Affiliation(s)
- Ayşe Handan Dökmeci
- School of Health, Department of Emergency and Disaster Management, Tekirdag Namik Kemal University, 59030, Tekirdağ, Turkey
| | - İhsan Karaboğa
- School of Health, Department of Emergency and Disaster Management, Tekirdag Namik Kemal University, 59030, Tekirdağ, Turkey.
| | - Savaş Güzel
- Faculty of Medicine, Department of Medical Biochemistry, Tekirdag Namik Kemal University, Tekirdağ, Turkey
| | - Zeynep Fidanol Erboğa
- Faculty of Medicine, Department of Histology and Embryology, Tekirdag Namik Kemal University, Tekirdağ, Turkey
| | - Ahsen Yılmaz
- Faculty of Medicine, Department of Medical Biochemistry, Tekirdag Namik Kemal University, Tekirdağ, Turkey
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Analysis of Indirect Biomarkers of Effect after Exposure to Low Doses of Bisphenol A in a Study of Successive Generations of Mice. Animals (Basel) 2022; 12:ani12030300. [PMID: 35158624 PMCID: PMC8833323 DOI: 10.3390/ani12030300] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 01/14/2022] [Accepted: 01/22/2022] [Indexed: 12/29/2022] Open
Abstract
Simple Summary Living beings are constantly and inadvertently exposed to a series of environmental and food pollutants, triggering effects on health that are transmitted over generations. Bisphenol A is a compound produced in large amounts world-wide and used in the manufacture of plastic containers and other utensils for daily use. It is an environmental and food pollutant with a demonstrated capacity to produce effects on the health of organisms exposed to it. The objective of our study was to identify possible indirect biomarkers of effect by means of the analysis of the blood biochemistry, and of certain reproductive parameters of animals exposed to Bisphenol A in doses considered to be safe over different generations. Our results did not show any modifications in the reproduction parameters evaluated, such as the duration of the estrous cycle, the size of the litters, or the percentage of the young alive at weaning time. However, they showed that there were alterations in biochemical parameters like glucose, total proteins, and albumin, which could therefore, be regarded as indirect indicators of an early effect of alterations in health caused by this compound. Abstract Bisphenol A (BPA) is considered as being an emerging pollutant, to which both animal and human populations are continuously and inadvertently exposed. The identification of indirect biomarkers of effect could be a key factor in determining early adverse outcomes from exposure to low doses of BPA. Thus, this study on mice aims to evaluate and identify indirect biomarkers of effect through the analysis of their blood biochemistry, and of certain reproduction parameters after exposure to different BPA concentrations (0.5, 2, 4, 50, and 100 µg/kg BW/day) in drinking water over generations. Our results showed that there were no modifications in the reproductive parameters evaluated, like estrous cycle duration, litter size, or the percentage of the young alive at reaching the weaning stage, at the exposure levels evaluated. However, there were modifications in the biochemical parameters, e.g., alterations in the glucose levels, that increased significantly (p < 0.05) in the breeders at the higher exposure doses (50 and 100 µg/kg BW/day in F1; 50 µg/kg BW/day in F2 and 100 µg/kg BW/day in F3), that would suggest that the BPA could induce hyperglycemia and its complications in adult animals, probably due to some damage in the pancreas cells; albumin, that increased in the breeders exposed to the highest dose in F1 and F3, inferring possible hepatic alterations. Further, total proteins showed a diminution in their values in F1 and F2, except the group exposed to 100 µg/kg BW/day, whereas in F3 the values of this parameter increased with respect to the control group, this aspect likely being related to a possible hepatic and renal alteration. Based on these results, glucose, albumin, and total proteins could initially be considered as early indicators of indirect effect after prolonged exposure to low BPA doses over generations.
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Tang H, Rising HH, Majji M, Brown RD. Long-Term Space Nutrition: A Scoping Review. Nutrients 2021; 14:194. [PMID: 35011072 PMCID: PMC8747021 DOI: 10.3390/nu14010194] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 12/23/2021] [Accepted: 12/28/2021] [Indexed: 01/30/2023] Open
Abstract
This scoping review aimed to identify current evidence and gaps in the field of long-term space nutrition. Specifically, the review targeted critical nutritional needs during long-term manned missions in outer space in addition to the essential components of a sustainable space nutrition system for meeting these needs. The search phrase "space food and the survival of astronauts in long-term missions" was used to collect the initial 5432 articles from seven Chinese and seven English databases. From these articles, two independent reviewers screened titles and abstracts to identify 218 articles for full-text reviews based on three themes and 18 keyword combinations as eligibility criteria. The results suggest that it is possible to address short-term adverse environmental factors and nutritional deficiencies by adopting effective dietary measures, selecting the right types of foods and supplements, and engaging in specific sustainable food production and eating practices. However, to support self-sufficiency during long-term space exploration, the most optimal and sustainable space nutrition systems are likely to be supported primarily by fresh food production, natural unprocessed foods as diets, nutrient recycling of food scraps and cultivation systems, and the establishment of closed-loop biospheres or landscape-based space habitats as long-term life support systems.
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Affiliation(s)
- Hong Tang
- College of Landscape and Tourism, Gansu Agricultural University, Lanzhou 730070, China;
| | - Hope Hui Rising
- Department of Landscape Architecture and Urban Planning, Texas A&M University, College Station, TX 77843, USA;
| | - Manoranjan Majji
- Department of Aerospace Engineering, Texas A&M University, College Station, TX 77843, USA;
| | - Robert D. Brown
- Department of Landscape Architecture and Urban Planning, Texas A&M University, College Station, TX 77843, USA;
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Schnegelberger RD, Lang AL, Arteel GE, Beier JI. Environmental toxicant-induced maladaptive mitochondrial changes: A potential unifying mechanism in fatty liver disease? Acta Pharm Sin B 2021; 11:3756-3767. [PMID: 35024304 PMCID: PMC8727895 DOI: 10.1016/j.apsb.2021.09.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 06/29/2021] [Accepted: 08/19/2021] [Indexed: 12/14/2022] Open
Abstract
Occupational and environmental exposures to industrial chemicals are well known to cause hepatotoxicity and liver injury. However, despite extensive evidence showing that exposure can lead to disease, current research approaches and regulatory policies fail to address the possibility that subtle changes caused by low level exposure to chemicals may also enhance preexisting conditions. In recent years, the conceptual understanding of the contribution of environmental chemicals to liver disease has progressed significantly. Mitochondria are often target of toxicity of environmental toxicants resulting in multisystem disorders involving different cells, tissues, and organs. Here, we review persistent maladaptive changes to mitochondria in response to environmental toxicant exposure as a mechanism of hepatotoxicity. With better understanding of the mechanism(s) and risk factors that mediate the initiation and progression of toxicant-induced liver disease, rational targeted therapy can be developed to better predict risk, as well as to treat or prevent this disease.
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Affiliation(s)
- Regina D. Schnegelberger
- Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Anna L. Lang
- Department of Neurology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Gavin E. Arteel
- Department of Medicine, Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh, Pittsburgh, PA 15213, USA
- Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Juliane I. Beier
- Department of Medicine, Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh, Pittsburgh, PA 15213, USA
- Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA 15213, USA
- Department of Environmental & Occupational Health, University of Pittsburgh, Pittsburgh, PA 15213, USA
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Mohsenzadeh MS, Razavi BM, Imenshahidi M, Tabatabaee Yazdi SA, Mohajeri SA, Hosseinzadeh H. Potential role of green tea extract and epigallocatechin gallate in preventing bisphenol A-induced metabolic disorders in rats: Biochemical and molecular evidence. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 92:153754. [PMID: 34607205 DOI: 10.1016/j.phymed.2021.153754] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 08/26/2021] [Accepted: 09/12/2021] [Indexed: 06/13/2023]
Abstract
BACKGROUND Bisphenol A (BPA) is an artificial chemical widely used in the production of polycarbonate plastics and epoxy resins. Accumulating evidence indicates that BPA exposure is associated with metabolic disorders. The beneficial effects of green tea and epigallocatechin gallate (EGCG), major catechin present in green tea, on alleviating BPA-induced metabolic disorders have been shown in various studies. PURPOSE Protective effects of green tea extract and EGCG on BPA-induced metabolic disorders and possible underlying mechanisms were investigated. METHODS Rats were randomly divided into control, green tea extract (50 and 100 mg/kg, IP), EGCG (20 and 40 mg/kg, IP), BPA (10 mg/kg, gavage), BPA plus green tea extract (25, 50, and 100 mg/kg, IP), BPA plus EGCG (10, 20, and 40 mg/kg, IP), and BPA plus vitamin E (200 IU/kg, IP). After two months, body weight, blood pressure, biochemical blood tests, hepatic malondialdehyde (MDA), and glutathione (GSH) were assessed. By enzyme-linked immunosorbent assay, serum levels of insulin, leptin, adiponectin, TNFα, and IL-6, and by western blotting, hepatic insulin signaling (IRS-1, PI3K, Akt) were measured. RESULTS BPA increased body weight, blood pressure, and MDA, decreased GSH, elevated serum levels of low-density lipoprotein cholesterol, total cholesterol, triglyceride, glucose, insulin, leptin, TNFα, IL-6, and liver enzymes including alanine aminotransferase and alkaline phosphatase, and lowered high-density lipoprotein cholesterol and adiponectin levels. In western blot, decreased phosphorylation of IRS-1, PI3K, and Akt was obtained. Administration of green tea extract, EGCG, or vitamin E with BPA reduced the detrimental effects of BPA. CONCLUSION These findings indicate that green tea extract and EGCG can be effective in preventing or reducing metabolic disorders induced by BPA linked to their antioxidant and anti-inflammatory activity, regulating the metabolism of lipids, and improving insulin signaling pathways.
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Affiliation(s)
- Mahdieh Sadat Mohsenzadeh
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Bibi Marjan Razavi
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Targeted Drug Delivery Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Mohsen Imenshahidi
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Seyed Ahmad Mohajeri
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Targeted Drug Delivery Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Hosseinzadeh
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
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Zhou Z, Goodrich JM, Strakovsky RS. Mitochondrial Epigenetics and Environmental Health: Making a Case for Endocrine Disrupting Chemicals. Toxicol Sci 2021; 178:16-25. [PMID: 32777053 DOI: 10.1093/toxsci/kfaa129] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Recent studies implicate mitochondrial dysfunction in the development and progression of numerous chronic diseases, which may be partially due to modifications in mitochondrial DNA (mtDNA). There is also mounting evidence that epigenetic modifications to mtDNA may be an additional layer of regulation that controls mitochondrial biogenesis and function. Several environmental factors (eg, smoking, air pollution) have been associated with altered mtDNA methylation in a handful of mechanistic studies and in observational human studies. However, little is understood about other environmental contaminants that induce mtDNA epigenetic changes. Numerous environmental toxicants are classified as endocrine disrupting chemicals (EDCs). Beyond their actions on hormonal pathways, EDC exposure is associated with elevated oxidative stress, which may occur through or result in mitochondrial dysfunction. Although only a few studies have assessed the impacts of EDCs on mtDNA methylation, the current review provides reasons to consider mtDNA epigenetic disruption as a mechanism of action of EDCs and reviews potential limitations related to currently available evidence. First, there is sufficient evidence that EDCs (including bisphenols and phthalates) directly target mitochondrial function, and more direct evidence is needed to connect this to mtDNA methylation. Second, these and other EDCs are potent modulators of nuclear DNA epigenetics, including DNA methylation and histone modifications. Finally, EDCs have been shown to disrupt several modulators of mtDNA methylation, including DNA methyltransferases and the mitochondrial transcription factor A/nuclear respiratory factor 1 pathway. Taken together, these studies highlight the need for future research evaluating mtDNA epigenetic disruption by EDCs and to detail specific mechanisms responsible for such disruptions.
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Affiliation(s)
- Zheng Zhou
- Department of Animal Sciences, Michigan State University, East Lansing, Michigan 48824
| | - Jaclyn M Goodrich
- Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan 48109
| | - Rita S Strakovsky
- Department of Food Science and Human Nutrition.,Institute for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824
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Paschoalini AL, Savassi LA, Weber AA, Moreira DP, Ribeiro YM, Rizzo E, Bazzoli N. Evaluation of the oestrogenic potential of oestrone and bisphenol-A on the reproduction of Astyanax bimaculatus males after subacute exposure. FISH PHYSIOLOGY AND BIOCHEMISTRY 2021; 47:797-810. [PMID: 33665751 DOI: 10.1007/s10695-021-00938-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 02/22/2021] [Indexed: 06/12/2023]
Abstract
In the last decades, oestrogenic compounds have often been reported in environmentally relevant concentrations in aquatic environments around the world. Most laboratory studies of oestrogens try to understand the effects of a single contaminant, but in natural environments, the effects may be quite different due to interactions with other compounds. The present study aimed to compare the action of oestrone (E1) and bisphenol-A (BPA), acting singularly and in combination, on the spermatogenesis of Astyanax bimaculatus. After exposure to 100 ng/L of E1, BPA and a mixture of the two for 15 days, our results showed that E1 and the E1 + BPA mixture significantly altered the number of spermatogenic cells. BPA presented high cytotoxicity when compared to other treatments. Analysis of the two oestrogenic compounds suggests that the E1 + BPA mixture has no additive or synergistic effects. Together, the results of the present study indicate that endocrine-disrupting chemicals (EDCs) analysed alone may behave differently than when administered with other substances.
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Affiliation(s)
- Alessandro Loureiro Paschoalini
- Departamento de Morfologia do Instituto de Ciências Biológicas, Universdidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil
- Programa de Pós-Graduação de Biologia de Vertebrados, Pontificia Universidade Católica de Minas Gerais, Belo Horizonte, Minas Gerais, 30535-610, Brazil
| | - Lourenço Almeida Savassi
- Departamento de Morfologia do Instituto de Ciências Biológicas, Universdidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil
| | - André Alberto Weber
- Departamento de Morfologia do Instituto de Ciências Biológicas, Universdidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil
- Department of Pharmacology, Robert Tukey Lab, University of California, San Diego, CA, USA
| | - Davidson Peruci Moreira
- Departamento de Morfologia do Instituto de Ciências Biológicas, Universdidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil
| | - Yves Moreira Ribeiro
- Departamento de Morfologia do Instituto de Ciências Biológicas, Universdidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil
| | - Elizete Rizzo
- Departamento de Morfologia do Instituto de Ciências Biológicas, Universdidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil
| | - Nilo Bazzoli
- Programa de Pós-Graduação de Biologia de Vertebrados, Pontificia Universidade Católica de Minas Gerais, Belo Horizonte, Minas Gerais, 30535-610, Brazil.
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Tonini C, Segatto M, Bertoli S, Leone A, Mazzoli A, Cigliano L, Barberio L, Mandalà M, Pallottini V. Prenatal Exposure to BPA: The Effects on Hepatic Lipid Metabolism in Male and Female Rat Fetuses. Nutrients 2021; 13:1970. [PMID: 34201166 PMCID: PMC8227982 DOI: 10.3390/nu13061970] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/01/2021] [Accepted: 06/04/2021] [Indexed: 12/16/2022] Open
Abstract
Bisphenol A (BPA) is an organic chemical compound widely used for manufacturing plastics. BPA exposure originates principally from the diet, but it can also originate from dermal contact. In over 90% of individuals, including pregnant women, BPA is detectable in several body fluids. The effects of this exposure on the fetus are under active investigation in several research laboratories. The aim of our work was to study the impact of prenatal exposure to BPA in the liver of rat fetuses from a sex-dependent point of view. We particularly investigated the effects of prenatal BPA exposure on hepatic lipids because of their crucial role, not only for the liver, but also for the whole-body functions. Our results demonstrate that the liver of rat fetuses, in utero exposed to a very low dose of BPA (2.5 µg/kg/day), displays significant modulations with regard to proteins involved in cholesterol and fatty acid biosynthesis and trafficking. Moreover, an impact on inflammatory process has been observed. All these effects are dependent on sex, being observable only in female rat fetuses. In conclusion, this work demonstrates that maternal exposure to BPA compromises hepatic lipid metabolism in female offspring, and it also reveals the perspective impact of BPA on human health at doses currently considered safe.
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Affiliation(s)
- Claudia Tonini
- Department of Science, University Roma Tre, Viale Marconi 446, 00146 Rome, Italy;
| | - Marco Segatto
- Department of Biosciences and Territory, University of Molise, Contrada Fonte Lappone, 86090 Pesche, Italy;
| | - Simona Bertoli
- International Center for the Assessment of Nutritional Status (ICANS), Department of Food Environmental and Nutritional Sciences (DeFENS), University of Milan, Via Mangiagalli 25, 20133 Milan, Italy; (S.B.); (A.L.)
- Lab of Nutrition and Obesity Research, Istituto Auxologico Italiano, IRCCS, 20100 Milan, Italy
| | - Alessandro Leone
- International Center for the Assessment of Nutritional Status (ICANS), Department of Food Environmental and Nutritional Sciences (DeFENS), University of Milan, Via Mangiagalli 25, 20133 Milan, Italy; (S.B.); (A.L.)
| | - Arianna Mazzoli
- Department of Biology, University of Naples Federico II, Complesso Universitario Monte Sant’Angelo, Via Cinthia—Edificio 7, 80126 Naples, Italy; (A.M.); (L.C.)
| | - Luisa Cigliano
- Department of Biology, University of Naples Federico II, Complesso Universitario Monte Sant’Angelo, Via Cinthia—Edificio 7, 80126 Naples, Italy; (A.M.); (L.C.)
| | - Laura Barberio
- Department of Biology, Ecology and Earth Science, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy; (L.B.); (M.M.)
| | - Maurizio Mandalà
- Department of Biology, Ecology and Earth Science, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy; (L.B.); (M.M.)
| | - Valentina Pallottini
- Department of Science, University Roma Tre, Viale Marconi 446, 00146 Rome, Italy;
- Neuroendocrinology Metabolism and Neuropharmacology Unit, IRCSS Fondazione Santa Lucia, Via del Fosso Fiorano 64, 00143 Rome, Italy
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Ahmed Zaki MS, Haidara MA, Abdallaa AM, Mohammed H, Sideeg AM, Eid RA. Role of dietary selenium in alleviating bisphenol A toxicity of liver albino rats: Histological, ultrastructural, and biomarker assessments. J Food Biochem 2021; 45:e13725. [PMID: 33847390 DOI: 10.1111/jfbc.13725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 03/22/2021] [Accepted: 03/26/2021] [Indexed: 02/05/2023]
Abstract
Bisphenol A (BPA) is used as a plasticizer in polycarbonate plastics. It has been used in consumer products and epoxy resins for decades as protective coatings and linings for food and beverage bottles. This can trigger human reactions to BPA which interferes with estrogen receptors. Our study explored the ameliorative effects of selenium (Se) in male rats on liver damage caused by BPA. Rats were divided into four groups at random: The first one obtained olive oil and acted as a control. Se (0.5 mg/kg diet) was given for the second group. The third one was treated with BPA (10 mg/kg body weight/day) orally. Concomitantly Se (0.5 mg/kg diet) and BPA (10 mg/kg body weight/day) were given orally in the fourth one. Liver specimens were prepared for light, electron microscopes and the serum samples were screened for biochemical markers. In the BPA received group, histological findings indicated apoptotic hepatic histological changes such as sinusoidal congestion, cytoplasmic vacuolation and leukocyte infiltration. Ultrastructurally, the same group had mitochondrial degeneration, rough endoplasmic reticulum swelling, and nuclear pyknosis, as well as fat droplet deposition and lysosome enhancement. Liver enzymes: In the BPA group, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been substantially increased. Moreover, histological and ultrastructural improvements were seen in the rat population treated with BPA and Se, whereas ALT and AST levels were lowered and malondialdehyde (MDA), glutathione peroxidase (GPx), human C reactive protein (hCRP), and the serum levels of interleukin-6 (IL-6) were significantly modulated. PRACTICAL APPLICATIONS: Bisphenol A (BPA) is used in the manufacturing of polycarbonate plastic (e.g., water bottles, baby bottles) and epoxy resins (e.g., inner coating in metallic food cans). It is a non-polymer preservative for other plastics, one of the contaminants of the atmosphere and a common endocrine estrogenic disruptor. Our study explored the ameliorative effects of selenium (Se) in male rats on liver damage caused by BPA. Rats were divided into four groups at random: The first one obtained olive oil and acted as a control. Se (0.5 mg/kg diet) was given for the second group. The third one was treated with BPA (10 mg/kg body weight/day) orally. Concomitant Se (0.5 mg/kg diet) and BPA (10 mg/kg body weight/day) were given in the fourth one. Liver specimens were prepared for light, electron microscopes and the serum samples were screened for biochemical markers.
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Affiliation(s)
- Mohamed Samir Ahmed Zaki
- Anatomy Department, College of Medicine, King Khalid University, Abha, Saudi Arabia
- Histology Department, College of Medicine, Zagazig University, Zagazig, Egypt
| | - Mohamed A Haidara
- Physiology Department, Kasr Al-Aini Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Asim M Abdallaa
- Anatomy Department, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Heitham Mohammed
- Anatomy Department, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Abulqasim M Sideeg
- Anatomy Department, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Refaat A Eid
- Pathology Department, College of Medicine, King Khalid University, Abha, Saudi Arabia
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50
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Khan NG, Correia J, Adiga D, Rai PS, Dsouza HS, Chakrabarty S, Kabekkodu SP. A comprehensive review on the carcinogenic potential of bisphenol A: clues and evidence. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2021; 28:19643-19663. [PMID: 33666848 PMCID: PMC8099816 DOI: 10.1007/s11356-021-13071-w] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 02/17/2021] [Indexed: 04/12/2023]
Abstract
Bisphenol A [BPA; (CH3)2C(C6H4OH)2] is a synthetic chemical used as a precursor material for the manufacturing of plastics and resins. It gained attention due to its high chances of human exposure and predisposing individuals at extremely low doses to diseases, including cancer. It enters the human body via oral, inhaled, and dermal routes as leach-out products. BPA may be anticipated as a probable human carcinogen. Studies using in vitro cell lines, rodent models, and epidemiological analysis have convincingly shown the increasing susceptibility to cancer at doses below the oral reference dose set by the Environmental Protection Agency for BPA. Furthermore, BPA exerts its toxicological effects at the genetic and epigenetic levels, influencing various cell signaling pathways. The present review summarizes the available data on BPA and its potential impact on cancer and its clinical outcome.
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Affiliation(s)
- Nadeem Ghani Khan
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Jacinta Correia
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Divya Adiga
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Padmalatha Satwadi Rai
- Department of Biotechnology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Herman Sunil Dsouza
- Department of Radiation Biology and Toxicology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Sanjiban Chakrabarty
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
- Center for DNA repair and Genome Stability (CDRGS), Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Shama Prasada Kabekkodu
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
- Center for DNA repair and Genome Stability (CDRGS), Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
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