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Navarro-Cruz AR, Juárez-Serrano D, Cesar-Arteaga I, Kammar-García A, Guevara-Díaz JA, Vera-López O, Lazcano-Hernández M, Pérez-Xochipa I, Segura-Badilla O. Oral administration of resveratrol reduces oxidative stress generated in the hippocampus of Wistar rats in response to consumption of ethanol. Front Behav Neurosci 2024; 17:1304006. [PMID: 38274548 PMCID: PMC10810024 DOI: 10.3389/fnbeh.2023.1304006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Accepted: 12/20/2023] [Indexed: 01/27/2024] Open
Abstract
Introduction Chronic ethanol intake has been found to favor hippocampal deterioration and alter neuronal morphological maturation; resveratrol has been suggested as an antioxidant that may counteract these effects. The objective of this study was to analyze the effect of resveratrol on oxidative stress markers, endogenous antioxidant system in the hippocampus, and the behavior of male Wistar rats administered different concentrations of ethanol. Methods The animals, at 3 months old, were randomly distributed into 11 study groups (n = 6/group), orally administered (5 days on, 2 days off) with water (control), ethanol (10, 20, 30, 40 or 50%), or ethanol (10, 20, 30, 40 or 50%) plus resveratrol (10 mg/Kg/day) for 2 months. Subsequently, the production of nitrites, malondialdehyde, and 4-hydroxy-alkenal (HNE) and the enzymatic activity of catalase and superoxide dismutase (SOD) were quantified. Results The levels of nitric oxide and lipid peroxidation products were significantly increased in each ethanol concentration and were statistically different compared to the control group; however, resveratrol significantly reduced oxidative stress caused by high ethanol concentration. The SOD and CAT did not present significant changes with respect to the controls in any of the study groups. In the different concentrations of ethanol used, GR increases significantly in the groups administered with resveratrol but not GPx. Resveratrol was shown to maintain the results similar to the control at most ethanol concentrations. Discussion Our results suggest that resveratrol prevents oxidative stress induced by ethanol in the hippocampus by decreasing cellular lipid peroxidation, but does not prevent the activation of catalase or SOD enzymes; however, allows glutathione to be kept active and in adequate concentrations in its reduced form and avoids alterations in the locomotor system.
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Affiliation(s)
- Addí Rhode Navarro-Cruz
- Departamento de Bioquímica-Alimentos, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico
| | - Daniel Juárez-Serrano
- Departamento de Bioquímica-Alimentos, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico
| | - Ivan Cesar-Arteaga
- Departamento de Bioquímica-Alimentos, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico
| | - Ashuin Kammar-García
- Dirección de Investigación, Instituto Nacional de Geriatría, Mexico City, Mexico
| | | | - Obdulia Vera-López
- Departamento de Bioquímica-Alimentos, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico
| | - Martin Lazcano-Hernández
- Departamento de Bioquímica-Alimentos, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico
| | - Ivonne Pérez-Xochipa
- Departamento de Bioquímica-Alimentos, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico
| | - Orietta Segura-Badilla
- Departamento de Nutrición y Salud Pública, Facultad de Ciencias de la Salud y de los Alimentos, Universidad del Bío-Bío, Chillán, Chile
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Anees S, Ahmad M, Ashraf S, Bhat AH, Hamid R, Ganie SA. Bioactive fractions from Allium humile alleviate the risk of high fat diet induced atherosclerosis in albino Wistar rats by inhibiting protein kinase C. Fitoterapia 2024; 172:105775. [PMID: 38097019 DOI: 10.1016/j.fitote.2023.105775] [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: 08/23/2023] [Revised: 12/07/2023] [Accepted: 12/07/2023] [Indexed: 12/19/2023]
Abstract
Atherosclerosis is a global concern that worsens with age, and plants that are effective medicinal herbs can give a viable alternative. PKC is a key factor in cardiovascular and other disorders; targeting it can reduce the risk of these diseases. We evaluated Allium humile for PKC inhibition and therapeutic efficacy against atherosclerosis. Soxhlet extraction was done to obtain extracts (hexane, ethyl acetate, methanol, ethanol and aqueous) and then tested for DPPH radical scavenging and PKC inhibitory activity. The methanolic extract was more active than the other extracts, so it was subjected to column chromatography, and seventeen fractions were obtained. Only 11, 12, and 15 showed good activity against PKC. Wistar rats were divided into six groups and each group received high fat diet for 30 days. Then the three potent fractions (10 mg/kg) were administered for 15 days along with high fat diet. Fraction II had the highest effectiveness (P < 0.0001) in decreasing lipid levels, lipid peroxidation, reducing IL-6 and TNF-α expression, and raising nitric oxide. This also demonstrated a decrease in PKC activity, as well as a decrease in the formation of the lipoidal layer in the aorta wall and rupture of the intima and media as validated by histological analysis. The two compounds, phytol acetate and cyanidin 3-(6″-o-malonyllaminaribioside) were characterised in fraction II by NMR and HRMS and cyanidin 3-(6″-o-malonyllaminaribioside) inhibited PKC more efficiently. Thus, Allium humile has strong anti-atherogenic activity as well as the ability to inhibit PKC both in vitro and in vivo.
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Affiliation(s)
- Suhail Anees
- Department of Clinical Biochemistry, University of Kashmir, Srinagar, India
| | - Muzaffar Ahmad
- Department of Biochemistry, University of Kashmir, Srinagar, India
| | - Suhail Ashraf
- Department of Clinical Biochemistry, University of Kashmir, Srinagar, India
| | | | - Rabia Hamid
- Department of Nanotechnology, University of Kashmir, Srinagar, India.
| | - Showkat Ahmad Ganie
- Department of Clinical Biochemistry, University of Kashmir, Srinagar, India.
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Roy A, Roy M, Gacem A, Datta S, Zeyaullah M, Muzammil K, Farghaly TA, Abdellattif MH, Yadav KK, Simal-Gandara J. Role of bioactive compounds in the treatment of hepatitis: A review. Front Pharmacol 2022; 13:1051751. [PMID: 36618936 PMCID: PMC9810990 DOI: 10.3389/fphar.2022.1051751] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Accepted: 11/24/2022] [Indexed: 12/24/2022] Open
Abstract
Hepatitis causes liver infection leading to inflammation that is swelling of the liver. They are of various types and detrimental to human beings. Natural products have recently been used to develop antiviral drugs against severe viral infections like viral hepatitis. They are usually extracted from herbs or plants and animals. The naturally derived compounds have demonstrated significant antiviral effects against the hepatitis virus and they interfere with different stages of the life cycle of the virus, viral release, replication, and its host-specific interactions. Antiviral activities have been demonstrated by natural products such as phenylpropanoids, flavonoids, xanthones, anthraquinones, terpenoids, alkaloids, aromatics, etc., against hepatitis B and hepatitis C viruses. The recent studies conducted to understand the viral hepatitis life cycle, more effective naturally derived drugs are being produced with a promising future for the treatment of the infection. This review emphasizes the current strategies for treating hepatitis, their shortcomings, the properties of natural products and their numerous types, clinical trials, and future prospects as potential drugs.
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Affiliation(s)
- Arpita Roy
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, India,*Correspondence: Arpita Roy, ; Jesus Simal-Gandara,
| | - Madhura Roy
- Centre for Translational and Clinical Research, School of Chemical and Life Sciences, Jamia Hamdard University, New Delhi, India
| | - Amel Gacem
- Department of Physics, Faculty of Sciences, University 20 Août 1955, Skikda, Algeria
| | - Shreeja Datta
- Biotechnology Department, Delhi Technological University, Rohini, India
| | - Md. Zeyaullah
- Department of Basic Medical Science, College of Applied Medical Sciences, Khamis Mushait Campus, King Khalid University, Abha, Saudi Arabia
| | - Khursheed Muzammil
- Department of Public Health, College of Applied Medical Sciences, Khamis Mushait Campus, King Khalid University, Abha, Saudi Arabia
| | - Thoraya A. Farghaly
- Department of Chemistry, Faculty of Applied Science, Umm Al‐Qura University, Makkah, Saudi Arabia
| | - Magda H. Abdellattif
- Department of Chemistry, College of Science, Taif University, Taif, Saudi Arabia
| | - Krishna Kumar Yadav
- Faculty of Science and Technology, Madhyanchal Professional University, Bhopal, India
| | - Jesus Simal-Gandara
- Nutrition and Bromatology Group, Analytical and Food Chemistry Department, Faculty of Science, Universidade de Vigo, Ourense, Spain,*Correspondence: Arpita Roy, ; Jesus Simal-Gandara,
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WANG J, GE Q, LI C, MA T, FANG Y, SUN X. Comparative study on the impact on mouse livers of different amounts of Chinese Baijiu, beer, and wine consumption. FOOD SCIENCE AND TECHNOLOGY 2022. [DOI: 10.1590/fst.65022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Affiliation(s)
| | - Qian GE
- Northwest A&F University, China; Ningxia Academy of Agricultural Sciences, China
| | - Caihong LI
- Ningxia Academy of Agricultural Sciences, China
| | | | | | - Xiangyu SUN
- Northwest A&F University, China; Ningxia Academy of Agricultural Sciences, China
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Chupradit S, Bokov D, Zamanian MY, Heidari M, Hakimizadeh E. Hepatoprotective and therapeutic effects of resveratrol: A focus on anti-inflammatory and anti- oxidative activities. Fundam Clin Pharmacol 2021; 36:468-485. [PMID: 34935193 DOI: 10.1111/fcp.12746] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Revised: 11/16/2021] [Accepted: 12/17/2021] [Indexed: 11/26/2022]
Abstract
Being the most essential organ in the body, the liver performs critical functions. Hepatic disorders, such as alcoholic liver disease, hepatic steatosis, liver fibrosis, non-alcoholic fatty liver disease, hepatocellular carcinoma and hepatic failure, have an impact on the biochemical and physiological functions of the body. The main representative of the flavonoid subgroup of flavones, Resveratrol (RES), exhibits suitable pharmacological activities for treating various liver diseases, such as fatty hepatitis, liver steatosis, liver cancer and liver fibrosis. According to various studies, grapes and red wine are good sources of RES. RES has various health properties; it is anti-inflammatory, anti-apoptotic, anti-oxidative and hepatoprotective against several hepatic diseases and hepatoxicity. Therefore, we performed a thorough research and created a summary of the distinct targets of RES in various stages of liver diseases. We concluded that RES inhibited liver inflammation essentially by causing a significant decrease in the expression of various pro-inflammatory cytokines like TNF-α, IL-1α, IL-1β, and IL-6. It also inhibits the transcription factor nuclear NF-κB that brings about the inflammatory cascade. RES also inhibits the PI3K/Akt/mTOR pathway to induce apoptosis. Additionally, it reduces oxidative stress in hepatic tissue by markedly reducing MDA and NO contents, and significantly increasing the levels of CAT, SOD and reduced GSH, in addition to AST and ALT, against toxic chemicals like CC14, As2O3 and TTA. Due to its anti-oxidant, anti-inflammatory and anti-fibrotic properties, RES reduces liver injury markers. RES is safe natural antioxidant that provides pharmacological rectification of the hepatoxicity of toxic chemicals.
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Affiliation(s)
- Supat Chupradit
- Department of Occupational Therapy, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
| | - Dmitry Bokov
- Institute of Pharmacy, Sechenov First Moscow State Medical University, Moscow, Russian Federation.,Laboratory of Food Chemistry, Federal Research Center of Nutrition, Biotechnology and Food Safety, 2/14 Ustyinsky pr, Moscow, Russian Federation
| | - Mohammad Yassin Zamanian
- Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.,School of Nahavand Paramedical, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Mahsa Heidari
- Department of Biochemistry, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran
| | - Elham Hakimizadeh
- Physiology-Pharmacology Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
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Gündüz A, Yalçın E, Çavuşoğlu K. Combined toxic effects of aflatoxin B 2 and the protective role of resveratrol in Swiss albino mice. Sci Rep 2021; 11:18081. [PMID: 34508115 PMCID: PMC8433416 DOI: 10.1038/s41598-021-95879-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 07/21/2021] [Indexed: 02/08/2023] Open
Abstract
In this study, the toxic effects of aflatoxin B2 (AFB2) on Swiss albino mice and the protective effects of resveratrol were investigated. Physiological (body weight, liver and kidney weight), biochemical (aspartate aminotransferase-AST, alanine transaminase-ALT, blood urea nitrogen-BUN, creatinine, malondialdehyde-MDA and glutathione-GSH) and cytogenetic parameters (micronucleus-MN in buccal epithelium, erythrocyte and leukocyte cells and chromosomal aberrations-CAs) were used to determine the toxic effects. Additionally, scavenging effects of resveratrol against superoxide, hydrogen peroxide (H2O2) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals were also investigated. In experimental period, mice were divided into six groups and the groups were treated with tap water, 10 mg/kg b.w resveratrol, 20 mg/kg b.w resveratrol, 20 µg/kg b.w. AFB2, 10 mg/kg b.w resveratrol + 20 µg/kg b.w AFB2, 20 mg/kg b.w resveratrol + 20 µg/kg b.w AFB2, respectively. As a result, the scavenging effects of resveratrol increased with increasing dose and the superoxide, H2O2 and DPPH radical scavenging activity of resveratrol were 74.9%, 79.1% and 49.2%, respectively. AFB2 administration caused a significant decrease in physiological parameters, and these decreases regressed in AFB2 + resveratrol treated groups. Serum ALT and AST activities, BUN and creatinine levels were higher in the AFB2 treated group compared to the control group and serious abnormalities were found in MDA and GSH levels in the kidney and liver. In the group treated with AFB2 + 20 mg/kg resveratrol, ALT, AST, BUN and creatinine levels decreased significantly and GSH levels increased compared to only-AFB2 treated group. AFB2 triggered MN formation in buccal epithelium, erythrocyte and leukocyte cells and CAs in bone marrow cells. The application of 20 mg/kg resveratrol together with AFB2 was decreased the MN and CAs frequency. Resveratrol exhibited a recovery effect in the range of 40.9-80.5% against AFB2 toxicity in all tested parameters. In this study, it was determined that AFB2 caused serious changes in selected physiological, biochemical and cytogenetic parameters while resveratrol displayed a protective role against these toxic effects.
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Affiliation(s)
- Alperen Gündüz
- grid.411709.a0000 0004 0399 3319Department of Biology, Faculty of Science and Art, Giresun University, 28200 Giresun, Turkey
| | - Emine Yalçın
- grid.411709.a0000 0004 0399 3319Department of Biology, Faculty of Science and Art, Giresun University, 28200 Giresun, Turkey
| | - Kültiğin Çavuşoğlu
- grid.411709.a0000 0004 0399 3319Department of Biology, Faculty of Science and Art, Giresun University, 28200 Giresun, Turkey
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Comparison of malondialdehyde levels and superoxide dismutase activity in resveratrol and resveratrol/donepezil combination treatment groups in Alzheimer's disease induced rat model. 3 Biotech 2021; 11:329. [PMID: 34189010 PMCID: PMC8200337 DOI: 10.1007/s13205-021-02879-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Accepted: 06/02/2021] [Indexed: 01/18/2023] Open
Abstract
The aim of this study was to determine the malondialdehyde (MDA) level and superoxide dismutase (SOD) activity in colchicine induced Alzheimer’s disease (AD), resveratrol (RS) treated and RS + donepezil (DPZ) treated rat models. The objective was to compare the MDA level and SOD activity among these rat models. The present study included 3 months old male albino Wistar rats, which were in-house bred and weighting about 220–250 g. The rats were divided into nine subgroups which included control, sham, AD induced, RS treated and DPZ treated groups in different doses and combinations. The lipid peroxidation product for MDA in the brain homogenate was measured by estimating the levels of thiobarbituric acid reactive substance. Estimation of SOD was done by the method of autoxidation of pyrogallol by Marklund and Marklund. There was a marked increase in the MDA levels in AD induced group in comparison to the control group (p < 0.05). The SOD activity was higher in the RS 10 and RS 20 treated groups in contrast to the AD group (p < 0.05). In DPZ + RS group, there was a substantial increase in the SOD activity (p < 0.05). It is also observed that the RS 20 treatment group showed higher SOD activity than the RS 10 group (p < 0.05). This study showed that, AD induced group had elevated levels of MDA, which indicates the poor oxidative stress–defence mechanism. The RS 10 and RS 20 groups showed higher SOD activity in comparison to the AD group, which indicated the improved oxidative stress–defence mechanism. The RS + DPZ group showed higher SOD activity, indicating a synergistic effect of DPZ and RS.
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Perfilova VN, Kustova MV, Popova TA, Khusainova GH, Prokofiev II, Nesterova KI, Tyurenkov IN. Cardioprotective effects of a new glutamic acid derivative in chronic alcohol intoxication. Alcohol 2021; 93:1-10. [PMID: 33737055 DOI: 10.1016/j.alcohol.2021.01.006] [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: 06/09/2020] [Revised: 12/12/2020] [Accepted: 01/27/2021] [Indexed: 02/07/2023]
Abstract
Alcohol abuse is a risk factor for heart damage and deterioration of its inotropic function. Currently, there is no pathogenetic pharmacological treatment for alcohol-induced myocardial injury. Therefore, the study of drugs with cardioprotective action is of current interest. Our earlier studies of stress-induced heart damage showed that a new derivative of glutamic acid - glufimet - protects the myocardium's inotropic function and limits lipid peroxidation. Additionally, we found that it increases the activity of antioxidant enzymes and improves mitochondrial respiration. The purpose of our study was to assess the effect of glufimet on the heart after chronic alcohol intoxication (CAI). The comparison drug was mildronate, which possesses cardioprotective properties and is used to treat alcohol withdrawal. We conducted our study using female Wistar rats (10 months old, 280-320 g). CAI was simulated by replacing drinking water with a 10% ethanol solution sweetened with sucrose (50 g/L) over a period of 24 weeks. The day after the animals stopped ethanol solution drinking, the control group was injected intraperitoneally (i.p.) with a saline solution once a day for 14 days, while the experimental groups received glufimet (28.7 mg/kg) and the drug of comparison mildronate (50 mg/kg), respectively. After that, we studied the heart contractility by measuring volume load, adrenergic reactivity, and maximum isometric load. Under CAI, the control group showed significantly lower growth in left ventricular pressure (LVP), myocardium contraction rate, and relaxation rate during functional tests. Higher concentrations of LPO products (malondialdehyde) and low activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase), indicating a disturbance in mitochondrial respiration compared to the control group, were registered. While being treated with glufimet and mildronate, the animals demonstrated higher growth rates of myocardial contraction, myocardial relaxation, and LVP, compared to the control group. Mitochondrial functioning and activity of the antioxidant enzymes increased in the same group as well.
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Neurological Alterations and Testicular Damages in Aging Induced by D-Galactose and Neuro and Testicular Protective Effects of Combinations of Chitosan Nanoparticles, Resveratrol and Quercetin in Male Mice. COATINGS 2021. [DOI: 10.3390/coatings11040435] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Aging is a neurological disease that is afforded by incidence of oxidative stress. Chitosan has received global interests due to its wide medical uses. Quercetin (Q) is a bioflavonoid and widely distributed in vegetables and fruits. Resveratrol is considered as a potent antioxidant and is a component of a wide range of foods. The using of either chitosan nanopartciles (CH-NPs), querectin (Q), and resveratrol (RV) to reduce the oxidative stress and biochemical alterations on brain and testicular tissues induced by D-galactose (DG) (100 mg/Kg) were the aim of the present study. This study investigated the probable protective effects of CH-NPs in two doses (140,280 mg/Kg), Q (20 mg/Kg) and RV (20 mg/Kg), against DG induced aging and neurological alterations. Brain antioxidant capacity as malonaldehyde (MDA), catalase (CAT), and glutathione reductase (GRx), as well as histopathological damages of the brain and testicular tissues were measured. The DG treated group had significantly elevated the oxidative stress markers by 96% and 91.4% in brain and testicular tissues respectively and lower significantly the antioxidant enzyme activities of both brain and testicular tissues than those of the control group by 86.95%, 69.27%, 83.07%, and 69.43%. Groups of DG that treated with a combination of CH-NPs in two doses, Q and RV, the levels of oxidative stress marker declined significantly by 68.70%, 76.64% in brain tissues and by 74.07% and 76.61% in testicular tissues, and the enzymatic antioxidants increased significantly by 75.55%, 79.24%, 62.32%, and 61.97% as compared to the DG group. The present results indicate that CH-NPs, Q, and RV have protective effects against DG-induced brain and testis tissue damage at the biochemical and histopathological levels. Mechanisms of this protective effect of used compounds against neurological and testicular toxicity may be due to the enhanced brain and testis antioxidant capacities.
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The Role of Resveratrol in Liver Disease: A Comprehensive Review from In Vitro to Clinical Trials. Nutrients 2021; 13:nu13030933. [PMID: 33805795 PMCID: PMC7999728 DOI: 10.3390/nu13030933] [Citation(s) in RCA: 63] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 03/10/2021] [Accepted: 03/11/2021] [Indexed: 12/15/2022] Open
Abstract
Many studies have shown that resveratrol has a lot of therapeutic effects on liver disorders. Its administration can significantly increase the survival rate after liver transplantation, reduce fat deposition and ischemia-induced necrosis and apoptosis in Wistar rats. Resveratrol can provide Liver protection against chemical, cholestatic, and alcohol-mediated damage. It can improve glucose metabolism and lipid profile, reduce liver fibrosis, and steatosis. Additionally, it is capable of altering the fatty acid composition of the liver cells. Resveratrol may be a potential treatment option for the management of non-alcoholic fatty liver disease (NAFLD) due to its anti-inflammatory, antioxidant, and calorie-restricting effects. There are also studies that have evaluated the effect of resveratrol on lipid and liver enzyme profiles among patients with metabolic syndrome (MetS) and related disorders. Based on the extent of liver disease worldwide and the need to find new treatment possibilities, this review critically examines current in vitro and in vivo preclinical studies and human clinical studies related to liver protection.
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Hashemzaei M, Tabrizian K, Alizadeh Z, Pasandideh S, Rezaee R, Mamoulakis C, Tsatsakis A, Skaperda Z, Kouretas D, Shahraki J. Resveratrol, curcumin and gallic acid attenuate glyoxal-induced damage to rat renal cells. Toxicol Rep 2020; 7:1571-1577. [PMID: 33304826 PMCID: PMC7708762 DOI: 10.1016/j.toxrep.2020.11.008] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 11/09/2020] [Accepted: 11/17/2020] [Indexed: 12/12/2022] Open
Abstract
RES, CUR and GA protected renal cells from GO–induced cells death. RES, CUR and GA reduced formation of ROS. RES, CUR and GA diminished lipid peroxidation products. RES, CUR and GA repressed GO-induced mitochondrial membrane potential collapse. RES, CUR and GA decreased lysosomal membrane leakage in GO-treated cells. Glyoxal (GO), a by-product of glucose auto-oxidation, is involved in the glycation of proteins/ lipids and formation of advanced glycation (AGE) and lipoxidation (ALE) end products. AGE/ALE were shown to contribute to diabetic complications development/progression such as nephropathy. Diabetic nephropathy progression has an oxidative nature. Given the antioxidant effects of polyphenols, potential protective effects of resveratrol, curcumin and gallic acid, in rat renal cells treated with GO, were evaluated in the present work. According to our results, incubation of GO with the cells reduced their viability and led to membrane lysis, reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial membrane potential collapse, and lysosomal membrane leakage. These findings were prevented by pre-treatment with resveratrol, curcumin and gallic acid. Mitochondrial and lysosomal toxic interactions appear to worsen oxidative stress/cytotoxicity produced by GO. Resveratrol, curcumin and gallic acid inhibited ROS formation and attenuated GO-induced renal cell death.
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Affiliation(s)
- Mahmoud Hashemzaei
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran.,Toxicology and Addiction Research Center, Zabol University of Medical Sciences, Zabol, Iran
| | - Kaveh Tabrizian
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran.,Toxicology and Addiction Research Center, Zabol University of Medical Sciences, Zabol, Iran
| | - Zeinab Alizadeh
- Toxicology and Addiction Research Center, Zabol University of Medical Sciences, Zabol, Iran
| | - Sedigheh Pasandideh
- Toxicology and Addiction Research Center, Zabol University of Medical Sciences, Zabol, Iran
| | - Ramin Rezaee
- Clinical Research Unit, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Charalampos Mamoulakis
- Department of Urology, University General Hospital of Heraklion, University of Crete, Medical School, Heraklion, Crete, Greece
| | - Aristidis Tsatsakis
- Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, Heraklion, 71003, Greece
| | - Zoi Skaperda
- Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, 41500, Greece
| | - Demetrios Kouretas
- Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, 41500, Greece
| | - Jafar Shahraki
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran.,Toxicology and Addiction Research Center, Zabol University of Medical Sciences, Zabol, Iran
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The Modulatory Effect of Metformin on Ethanol-Induced Anxiety, Redox Imbalance, and Extracellular Matrix Levels in the Brains of Wistar Rats. J Mol Neurosci 2020; 70:1943-1961. [PMID: 32621100 DOI: 10.1007/s12031-020-01593-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2020] [Accepted: 05/13/2020] [Indexed: 01/14/2023]
Abstract
The study investigated the potential neuroprotective effects of metformin (MET) on alcohol-induced neurotoxicity in adult Wistar rats. The animals were randomized in four groups (n = 10): control, alcohol (ALC), ALC + MET, and MET. ALC (2 g/kg b.w.) and MET (200 mg/kg b.w.) were orally administered for 21 days, once daily. For the ALC + MET group, MET was administered 2 h after ALC treatment. On day 22, the open field test (OFT) and elevated plus maze (EPM) were performed. MET improved global activity and increased the time spent in unprotected open arms, decreased oxidative stress, both in the frontal lobe and in the hippocampus, and increased neuroglobin expression in the frontal cortex. Histopathologically, an increased neurosecretory activity in the frontal cortex in the ALC + MET group was noticed. Thus, our findings suggest that metformin has antioxidant and anxiolytic effects and may partially reverse the neurotoxic effects induced by ethanol.
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Jalili C, Farzaei MH, Roshankhah S, Salahshoor MR. Resveratrol attenuates malathion-induced liver damage by reducing oxidative stress. J Lab Physicians 2020; 11:212-219. [PMID: 31579256 PMCID: PMC6771320 DOI: 10.4103/jlp.jlp_43_19] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND: Malathion is an organophosphate insecticide which disrupts the antioxidant system of the body. Resveratrol is a phytoestrogen and antioxidant of the red grape. AIM AND OBJECTIVE: This study was designed to evaluate the effects of resveratrol against toxic effects of malathion to the liver of rats. MATERIALS AND METHODS: In this study, 48 male rats were randomly assigned to 8 groups: control normal (saline) and malathion control-treated groups (50 mg/kg), resveratrol groups (2, 8, and 20 mg/kg), and malathion + resveratrol-treated groups (2, 8, and 20 mg/kg). Treatments were administered intraperitoneally daily for 14 days. Griess technique was assessed for determined serum nitrite oxide level. Aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase concentrations were determined for liver functional disturbances. In addition, thiobarbituric acid reactive species, antioxidant capacity, the diameter of hepatocytes, and the central hepatic vein (CHV) were investigated. RESULTS: Malathion administration significantly improved liver malondialdehyde (MDA) and nitrite oxide level, the mean diameter of CHV and hepatocyte, and liver enzymes and decreased tissue ferric-reducing ability of plasma (FRAP) level compared to the normal control group (P < 0.01). The resveratrol and resveratrol + malathion treatments at all doses significantly reduced the mean diameter of hepatocyte and CHV, liver enzymes, kidney MDA, and nitrite oxide levels and increased tissue FRAP level compared to the malathion control group (P < 0.01). CONCLUSION: It seems that resveratrol administration improved liver injury induced by malathion in rats.
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Affiliation(s)
- Cyrus Jalili
- Department of Anatomical Sciences, Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mohammad Hosein Farzaei
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Shiva Roshankhah
- Department of Anatomical Sciences, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mohammad Reza Salahshoor
- Department of Anatomical Sciences, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran
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14
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Lee DH, Lee JS, Lee IH, Hong JT. Therapeutic potency of fermented field water-dropwort (Oenanthe javanica (Blume) DC.) in ethanol-induced liver injury. RSC Adv 2020; 10:1544-1551. [PMID: 35494709 PMCID: PMC9048287 DOI: 10.1039/c9ra08976d] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Accepted: 12/11/2019] [Indexed: 12/13/2022] Open
Abstract
Alcohol overconsumption and abuse leads to alcoholic liver disease (ALD), which is a major chronic liver disease worldwide. Field water-dropwort (Oenanthe javanica (Blume) DC.) is a small perennial herb and has been cultivated in Asia for thousands of years and traditionally used to treat various diseases including hepatitis, jaundice, hypertension and polydipsia, as well as its therapeutic benefits have been recognized for centuries in Asia. Although several studies have reported that water-dropwort extracts have pharmacological effects on various diseases, the pharmacological ability of fermented field water-dropwort in ALD is not reported yet. Thus, we investigated the effect of fermented field water-dropwort extracts (FDE) on chronic plus binge ethanol-induced liver injury. C57BL/6 male mice (9 weeks old) were fed on a Lieber–DeCarli diet containing 6.6% ethanol for 10 days with parallel saline or FDE orally administered each day. Ethanol-induced hepatic triglyceride (TG) levels and the mRNA levels of TG synthesis-related genes such as sterol regulatory element binding protein 1 (SREBP1), acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were decreased in the liver of mice with FDE administration. Moreover, FDE administered mice showed decreasing ethanol-induced oxidative stress such as increasing oxidised glutathione and lipid peroxidation in the liver. In primary hepatic cells, FDE treated cells exhibited decreased ethanol-induced lipid accumulation and the mRNA levels of TG synthesis-related genes, SREBP-1, ACC and FAS. In conclusions, FDE has the potential to be explored as a candidate treatment agent for ALD by inhibiting TG synthesis and blocking of oxidative stress. Alcohol overconsumption and abuse leads to alcoholic liver disease (ALD), which is a major chronic liver disease worldwide.![]()
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Affiliation(s)
- Dong Hun Lee
- College of Pharmacy and Medical Research Center
- Chungbuk National University
- Cheongju
- Republic of Korea
| | - Jong Sung Lee
- College of Pharmacy and Medical Research Center
- Chungbuk National University
- Cheongju
- Republic of Korea
| | - Il Ho Lee
- OSBio, Co. Ltd
- Cheongju
- Republic of Korea
| | - Jin Tae Hong
- College of Pharmacy and Medical Research Center
- Chungbuk National University
- Cheongju
- Republic of Korea
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15
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Influence of Resveratrol on Oxidation Processes and Lipid Phase Characteristics in Damaged Somatic Nerves. BIOMED RESEARCH INTERNATIONAL 2019; 2019:2381907. [PMID: 31886183 PMCID: PMC6927059 DOI: 10.1155/2019/2381907] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 10/06/2019] [Accepted: 10/28/2019] [Indexed: 12/31/2022]
Abstract
It has been shown that the intensification of oxidative processes is observed when somatic nerves of rats are damaged. Accumulation of malondialdehyde occurs, and the phase properties of the lipid bilayer change, especially in the distal part of the nerve. Under the same conditions, there are multidirectional changes in the activity of antioxidant enzymes, superoxide dismutase (SOD) activity decreases, and catalase (CAT) activity increases. Under the action of resveratrol, there is a decrease in the number of TBA-active products in both areas of the damaged nerve. Alongside resveratrol action, SOD and CAT activity tends to return towards the control values. Similar patterns are observed in the action of resveratrol on the phase states of lipids with the damage to somatic nerves. By summarizing the data obtained, it can be claimed that when the nerve is damaged, profound changes occur both in the lipid component and in the antioxidant system. Resveratrol has a stabilizing effect on the studied parameters, and a longer period of time is required for their complete recovery.
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16
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Lee DH, Han JH, Lee YS, Jung YS, Roh YS, Yun JS, Han SB, Hong JT. Chitinase-3-like-1 deficiency attenuates ethanol-induced liver injury by inhibition of sterol regulatory element binding protein 1-dependent triglyceride synthesis. Metabolism 2019; 95:46-56. [PMID: 30935969 DOI: 10.1016/j.metabol.2019.03.010] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Revised: 03/22/2019] [Accepted: 03/25/2019] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Alcohol overconsumption and abuse lead to alcoholic liver disease (ALD), which is a major chronic liver disease worldwide. Chitinase-3-like protein 1 (CHI3L1) have an important role in the pathogenesis of inflammatory disease. However, the role of CHI3L1 in ALD has not yet been reported. In the present study, we investigated the effect of CHI3L1 on chronic plus binge ethanol-induced liver injury. METHODS CHI3L1 knock out (KO) mice and their littermate control mice based on C57BL/6 (10-12 weeks old) were fed on a Lieber-DeCarli diet containing 6.6% ethanol for 10 days. And, CHI3L1 siRNA or CHI3L1 expressing vector was transfected HepG2 cells were treated with ethanol or without. RESULTS Ethanol-induced hepatic triglyceride (TG) levels and the mRNA levels of TG synthesis-related genes such as acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD1) were decreased in the liver of CHI3L1 knock out (KO) mice and the HepG2 cells transfected with CHI3L1 siRNA. Increased mRNA level and activation of SREBP1 which is transcription factor of ACC, FAS and SCD1 by ethanol feeding were reduced in the liver of ethanol-fed CHI3L1 KO mice. Moreover, ethanol-induced SREBP1 luciferase activity and mRNA level of SREBP1, ACC, FAS and SCD1 were also decreased in the HepG2 cells transfected with CHI3L1 siRNA, while those were further increased in the HepG2 cells treated with recombinant human CHI3L1. Furthermore, oxidative stress and up-regulated pro-inflammatory cytokines by ethanol were recovered in the liver of ethanol-fed CHI3L1 KO mice. CONCLUSION Our finding suggest that inhibition of CHI3L1 suppressed ethanol-induced liver injury through inhibition of TG synthesis, and the blocking of oxidative stress and hepatic inflammation induced SREBP1 activity could be significant.
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Affiliation(s)
- Dong Hun Lee
- College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 28160, Republic of Korea
| | - Ji Hye Han
- College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 28160, Republic of Korea
| | - Yong Sun Lee
- College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 28160, Republic of Korea
| | - Young Suk Jung
- College of Pharmacy, Pusan National University, 2, Busandaehak-ro 63beon gil, Geumjeong-gu, Busan 609-735, Republic of Korea
| | - Yoon Seok Roh
- College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 28160, Republic of Korea
| | - Jae Suk Yun
- College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 28160, Republic of Korea
| | - Sang Bae Han
- College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 28160, Republic of Korea
| | - Jin Tae Hong
- College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 28160, Republic of Korea.
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17
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Alamo A, Condorelli RA, Mongioì LM, Cannarella R, Giacone F, Calabrese V, La Vignera S, Calogero AE. Environment and Male Fertility: Effects of Benzo-α-Pyrene and Resveratrol on Human Sperm Function In Vitro. J Clin Med 2019; 8:jcm8040561. [PMID: 31027257 PMCID: PMC6518055 DOI: 10.3390/jcm8040561] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 04/12/2019] [Accepted: 04/19/2019] [Indexed: 12/13/2022] Open
Abstract
Lifestyle, cigarette smoking and environmental pollution have a negative impact on male fertility. Therefore, the aim of this study was to evaluate the in-vitro effects of benzo-α-pyrene (BaP) and aryl hydrocarbon receptor (AHR) agonists on motility and bio-functional sperm parameters. We further assessed whether resveratrol (RES), an AHR antagonist and antioxidant molecule, had any protective effect. To accomplish this, 30 normozoospermic, healthy, non-smoker men not exposed to BaP were enrolled. Spermatozoa of 15 men were incubated with increasing concentrations of BaP to evaluate its effect and to establish its dose response. Then, spermatozoa of the 15 other men were incubated with BaP (15 µM/mL), chosen according to the dose-response and/or RES to evaluate its antagonistic effects. The effects of both substances were evaluated after 3 h of incubation on total and progressive sperm motility and on the following bio-functional sperm parameters evaluated by flow cytometry: Degree of chromatin compactness, viability, phosphatidylserine externalization (PS), late apoptosis, mitochondrial membrane potential (MMP), DNA fragmentation, degree of lipoperoxidation (LP), and concentrations of mitochondrial superoxide anion. Benzo-α-pyrene decreased total and progressive sperm motility, impaired chromatin compactness, and increased sperm lipoperoxidation and mitochondrial superoxide anion levels. All these effects were statistically significant at the lowest concentration tested (15 µM/mL) and they were confirmed at the concentration of 45 µM/mL. In turn, RES was able to counteract the detrimental effects of BaP on sperm motility, abnormal chromatin compactness, lipid peroxidation, and mitochondrial superoxide. This study showed that BaP alters sperm motility and bio-functional sperm parameters and that RES exerts a protective effect on BaP-induced sperm damage.
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Affiliation(s)
- Angela Alamo
- Department of Clinical and Experimental Medicine, 95123 Catania, Italy.
| | | | - Laura M Mongioì
- Department of Clinical and Experimental Medicine, 95123 Catania, Italy.
| | | | - Filippo Giacone
- Department of Clinical and Experimental Medicine, 95123 Catania, Italy.
| | - Vittorio Calabrese
- Department of Biomedical and Biotechnological Sciences, 95123 Catania, Italy.
| | - Sandro La Vignera
- Department of Clinical and Experimental Medicine, 95123 Catania, Italy.
- CoHEAR, Research Center for Smoking Damage Reduction, University of Catania, 95123 Catania, Italy.
| | - Aldo E Calogero
- Department of Clinical and Experimental Medicine, 95123 Catania, Italy.
- CoHEAR, Research Center for Smoking Damage Reduction, University of Catania, 95123 Catania, Italy.
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18
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Revin VV, Pinyaev SI, Parchaykina MV, Revina ES, Maksimov GV, Kuzmenko TP. The Effect of Resveratrol on the Composition and State of Lipids and the Activity of Phospholipase A 2 During the Excitation and Regeneration of Somatic Nerves. Front Physiol 2019; 10:384. [PMID: 31057413 PMCID: PMC6482430 DOI: 10.3389/fphys.2019.00384] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Accepted: 03/21/2019] [Indexed: 12/27/2022] Open
Abstract
It has been shown that in the somatic nerve's lipids, both during excitation and transection, changes occur with the composition of individual phospholipids and in phospholipids fatty acids, which changes the phase state of the myelin and nerve fiber axolemma lipid bilayer. A main contribution in the nerve degenerative processes is dependent on the composition phospholipid's fatty acid changes during the activation of both Ca2+-dependent and Ca2+-independent phospholipase A2 forms. At the same time, we studded changes in phosphoinisitol (PI) and diacylglycerol (DAG), which depend on the phosphoinositide cycle function during nerve excitation and degeneration processes. It was found that myelin lipids and nerve fiber axolemmas are involved not only in the functioning of the peripheral nerves, but also the pathological processes underlying deep functional and structural disorders. The effect of resveratrol on regeneration processes in the damaged rat sciatic nerve has also been investigated.
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Affiliation(s)
- Victor Vasilevich Revin
- Department of Biotechnology, Bioengineering and Biochemistry, National Research Ogarev Mordovia State University, Saransk, Russia
| | - Sergey Ivanovich Pinyaev
- Department of Biotechnology, Bioengineering and Biochemistry, National Research Ogarev Mordovia State University, Saransk, Russia
| | - Marina Vladimirovna Parchaykina
- Department of Biotechnology, Bioengineering and Biochemistry, National Research Ogarev Mordovia State University, Saransk, Russia
| | - Elvira Sergeevna Revina
- Department of Biotechnology, Bioengineering and Biochemistry, National Research Ogarev Mordovia State University, Saransk, Russia
| | | | - Tatyana Pavlovna Kuzmenko
- Department of Biotechnology, Bioengineering and Biochemistry, National Research Ogarev Mordovia State University, Saransk, Russia
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19
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Rubio-Ruiz ME, Guarner-Lans V, Cano-Martínez A, Díaz-Díaz E, Manzano-Pech L, Gamas-Magaña A, Castrejón-Tellez V, Tapia-Cortina C, Pérez-Torres I. Resveratrol and Quercetin Administration Improves Antioxidant DEFENSES and reduces Fatty Liver in Metabolic Syndrome Rats. Molecules 2019; 24:E1297. [PMID: 30987086 PMCID: PMC6479544 DOI: 10.3390/molecules24071297] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Revised: 03/28/2019] [Accepted: 03/30/2019] [Indexed: 12/21/2022] Open
Abstract
Mixtures of resveratrol (RSV) + quercetin (QRC) have antioxidant properties that probably impact on fatty liver in metabolic syndrome (MS) individuals. Here, we study the effects of a mixture of RSV + QRC on oxidative stress (OS) and fatty liver in a rat model of MS. Weanling male Wistar rats were separated into four groups (n = 8): MS rats with 30% sucrose in drinking water plus RSV + QRC (50 and 0.95 mg/kg/day, respectively), MS rats without treatment, control rats (C), and C rats plus RSV + QRC. MS rats had increased systolic blood pressure, triglycerides, insulin levels, insulin resistance index homeostasis model (HOMA), adiponectin, and leptin. The RSV + QRC mixture compensated these variables to C values (p < 0.01) in MS rats. Lipid peroxidation and carbonylation were increased in MS. Total antioxidant capacity and glutathione (GSH) were decreased in MS and compensated in MS plus RVS + QRC rats. Catalase, superoxide dismutase isoforms, peroxidases, glutathione-S-transferase, glutathione reductase, and the expression of Nrf2 were decreased in MS and reversed in MS plus RVS + QRC rats (p < 0.01). In conclusion, the mixture of RSV + QRC has benefic effects on OS in fatty liver in the MS rats through the improvement of the antioxidant capacity and by the over-expression of the master factor Nrf2, which increases the antioxidant enzymes and GSH recycling.
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Affiliation(s)
- Maria Esther Rubio-Ruiz
- Department of Physiology, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico.
| | - Verónica Guarner-Lans
- Department of Physiology, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico.
| | - Agustina Cano-Martínez
- Department of Physiology, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico.
| | - Eulises Díaz-Díaz
- Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Vasco de Quiroga 15, Sección XVI, Tlalpan, Mexico City 14000, Mexico.
| | - Linaloe Manzano-Pech
- Department of Pathology, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico.
| | - Anel Gamas-Magaña
- Department of Physiology, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico.
| | - Vicente Castrejón-Tellez
- Department of Physiology, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico.
| | - Concepción Tapia-Cortina
- Colegio de Ciencias y Humanidades. Licenciatura en Promoción de la Salud. Academia de salud comunitaria. Universidad Autónoma de la Ciudad de México; Plantel San Lorenzo Tezonco, Mexico City 06720, Mexico.
| | - Israel Pérez-Torres
- Department of Pathology, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico.
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20
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Ali DA, Badr El-Din NK, Abou-El-magd RF. Antioxidant and hepatoprotective activities of grape seeds and skin against Ehrlich solid tumor induced oxidative stress in mice. ACTA ACUST UNITED AC 2019. [DOI: 10.1016/j.ejbas.2015.02.003] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Affiliation(s)
- Doaa A. Ali
- Department of Zoology, Faculty of Science, University of Mansoura, Mansoura, Egypt
| | | | - Rania F. Abou-El-magd
- Department of Medical Biology, Faculty of Medicine, Gazan University, Gazan, Saudi Arabia
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21
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Szkudelski T, Szkudelska K. Potential of resveratrol in mitigating metabolic disturbances induced by ethanol. Biomed Pharmacother 2018. [PMID: 29514131 DOI: 10.1016/j.biopha.2018.02.063] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023] Open
Abstract
Alcohol abuse is associated with numerous health problems, including metabolic disturbances and liver damage. Therefore, different compounds are continuously being tested to evaluate their potential effectiveness in reducing these harmful changes. Animal studies clearly show that resveratrol is capable of ameliorating some consequences of ethanol ingestion. Resveratrol is a naturally occurring diphenolic compound having pleiotropic, health-promoting properties. Its beneficial action have been also demonstrated in animal models with ethanol-induced metabolic disturbances and liver injury. In ethanol treated animals, resveratrol effectively reduced liver lipid accumulation. Moreover, this compound diminished necrosis of hepatocytes, and also reduced liver fibrosis. The hepatoprotective action of resveratrol is largely associated with its ant-oxidant and anti-inflammatory properties, and also covers changes in activities of some enzymes. It is known that this compound upregulates the adiponectin-SIRT1-AMPK signaling pathway in the liver. Resveratrol was also found to positively affect blood lipids in animals exposed to ethanol. Moreover, administration of resveratrol to animals with ethanol-induced hypoinsulinemia and insulin resistance was shown to alleviate these disturbances. These outcomes clearly indicate that resveratrol holds great potential to reduce some consequences of ethanol ingestion. However, human studies are required to fully assess its therapeutic value.
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Affiliation(s)
- Tomasz Szkudelski
- Department of Animal Physiology and Biochemistry Poznan University of Life Sciences, Wolynska 35, 60-637 Poznan, Poland
| | - Katarzyna Szkudelska
- Department of Animal Physiology and Biochemistry Poznan University of Life Sciences, Wolynska 35, 60-637 Poznan, Poland.
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22
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Aslankoc R, Gumral N, Saygin M, Senol N, Asci H, Cankara FN, Comlekci S. The impact of electric fields on testis physiopathology, sperm parameters and DNA integrity-The role of resveratrol. Andrologia 2018; 50:e12971. [PMID: 29411409 DOI: 10.1111/and.12971] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/26/2017] [Indexed: 12/14/2022] Open
Abstract
This study investigated the long-term effects of electric fields (EF) which might cause physiopathological or morphological changes in the testis tissues of rats. We assumed that using resveratrol (RES) might reduce harmful effects of the EF. Thirty-two male Wistar Albino rats were randomly divided into four groups with eight animals in each; control, EF, EF + RES and RES. Malondialdehyde (MDA), superoxide dismutase, catalase, glutathione peroxidase and histopathological parameters were evaluated in testis tissue. Epididymal sperm count, motility and DNA damage were studied. Total testosterone, follicle-stimulating hormone, luteinising hormone, estradiol and growth hormone levels were evaluated in the plasma samples. EF caused statistically significant increase in MDA levels, body weight and DNA damage. A significant decrease was detected in sperm count and motility. The histopathological examination of the testes showed the germ cell decrease in the seminiferous epithelium with oedema and vascular congestion in the interstitial tissue. In immunohistochemical examination, the increase in the apoptotic cells number was detected. RES partially ameliorated biochemical, histopathological and immunohistochemical findings in the EF + RES group. These findings clearly demonstrated that EF can cause damage in rat testis. RES can ameliorate the damage caused by EF.
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Affiliation(s)
- R Aslankoc
- Department of Physiology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey
| | - N Gumral
- Department of Physiology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey
| | - M Saygin
- Department of Physiology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey
| | - N Senol
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Suleyman Demirel University, Isparta, Turkey
| | - H Asci
- Department of Pharmacology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey
| | - F N Cankara
- Department of Pharmacology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey
| | - S Comlekci
- Department of Electronics and Communication Engineering, Faculty of Engineering, Suleyman Demirel University, Isparta, Turkey
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23
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Boyle M, Masson S, Anstee QM. The bidirectional impacts of alcohol consumption and the metabolic syndrome: Cofactors for progressive fatty liver disease. J Hepatol 2018; 68:251-267. [PMID: 29113910 DOI: 10.1016/j.jhep.2017.11.006] [Citation(s) in RCA: 105] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Revised: 10/30/2017] [Accepted: 11/01/2017] [Indexed: 12/12/2022]
Abstract
Current medical practice artificially dichotomises a diagnosis of fatty liver disease into one of two common forms: alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). Together, these account for the majority of chronic liver diseases worldwide. In recent years, there has been a dramatic increase in the prevalence of obesity and metabolic syndrome within the general population. These factors now coexist with alcohol consumption in a substantial proportion of the population. Each exposure sensitises the liver to the injurious effects of the other; an interaction that drives and potentially accelerates the genesis of liver disease. We review the epidemiological evidence and scientific literature that considers how alcohol consumption interacts with components of the metabolic syndrome to exert synergistic or supra-additive effects on the development and progression of liver disease, before discussing how these interactions may be addressed in clinical practice.
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Affiliation(s)
- Marie Boyle
- Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, United Kingdom
| | - Steven Masson
- Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, United Kingdom
| | - Quentin M Anstee
- Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, United Kingdom.
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24
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Özatik FY, Özatik O, Yiğitaslan S, Ünel ÇÇ, Erol K. Protective role of resveratrol on testicular germ cells in mice with testicular toxicity. Turk J Urol 2017; 43:444-450. [PMID: 29201506 DOI: 10.5152/tud.2017.34101] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2016] [Accepted: 04/18/2017] [Indexed: 11/22/2022]
Abstract
Objective The aim of the present study was to investigate the possible beneficial effects of resveratrol in mice subjected to vinyl cyclohexene dieposide (VCD) -induced testicular toxicity. Material and methods A total of thirty- six Swiss albino male mice aged 28-days were used in the present study. The study was composed of two stages where mice which received or did not receive VCD (320 mg/kg/day) were administered resveratrol. The animals were assigned into control and resveratrol-treated groups in the first stage and into groups of VCD- and VCD+resveratrol-treated groups in the second stage. At the end of the experiments, relative testicular weight (TW/BW) and dry/wet weight of testis (TDW/TWW) were calculated. Histological analysis by hematoxylin and eosin (H&E) staining and immunohistochemical staining by BAX and Bcl-2 were performed. Serum testosterone, LH and FSH levels were measured by a commercially available ELISA kit. Results Resveratrol caused a dose-dependent increase in TW/BW and decrease in TDW/TWW (p<0.05). Resveratrol at a dose of 20 mg/kg resulted in an improvement in testosterone, LH and FSH levels in mice with VCD-induced testicular toxicity (p<0.001). Resveratrol also improved apoptotic index and epithelial cell height of testicular seminipherous tubuli significantly after VCD exposure (p<0.001). Conclusion Results of the present study suggest that resveratrol can be used as a protective and/or therapeutic agent particularly for cases with male infertility caused by testicular toxicity.
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Affiliation(s)
| | - Orhan Özatik
- Department of Histology and Embriyology, Ahi Evran University School of Medicine, Kırsehir, Turkey
| | - Semra Yiğitaslan
- Department of Pharmacology, Eskişehir Osmangazi University School of Medicine, Eskişehir, Turkey
| | - Çiğdem Çengelli Ünel
- Department of Pharmacology, Eskişehir Osmangazi University School of Medicine, Eskişehir, Turkey
| | - Kevser Erol
- Department of Pharmacology, Eskişehir Osmangazi University School of Medicine, Eskişehir, Turkey
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25
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Hamza RZ, El-Shenawy NS. Anti-inflammatory and antioxidant role of resveratrol on nicotine-induced lung changes in male rats. Toxicol Rep 2017; 4:399-407. [PMID: 28959665 PMCID: PMC5615151 DOI: 10.1016/j.toxrep.2017.07.003] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2017] [Revised: 07/03/2017] [Accepted: 07/14/2017] [Indexed: 01/20/2023] Open
Abstract
Nicotine decreased the antioxidant capacities in male rats. The lung of nicotine-treated rats showed severe congestion of the alveolar lung tissues. Resveratrol exerts its protective effect by alleviating the extent of oxidative status induced by nicotine. Resveratrol improve the enzymatic/non-enzymatic antioxidant defense system in rats treated with combination of nicotine and resveratrol. Resveratrol decreases the pathological changes in animals against the lung damage caused by nicotine. Male albino rats of Wistar strain were injected intraperitoneally with nicotine or/and resveratrol for 4 weeks. Serum Interleukin-2, Interleukin-6, alpha-fetoprotein and tumor necrosis-alpha, as well as plasma 8-hydroxydeoxyguanosine of nicotine-treated rats were increased significantly. Myeloperoxidase, xanthine oxidase, nitric oxide, lipid peroxidation and total oxidative status of the lung in nicotine-treated rats were increased significantly, which were brought down to normal in resveratrol co-treated group. Endogenous antioxidant status as the activity of superoxide dismutase, catalase, glutathione peroxidase, and glucose-6-phosphate dehydrogenases were found to be decreased significantly in the lung of the nicotine-treated group, which were significantly raised in resveratrol-administered groups. The non-enzymatic antioxidants as total antioxidant and thiol levels were decreased significantly as the effect of nicotine that was effectively enhanced by resveratrol treatment. The lung of nicotine-treated rats showed severe congestion of the alveolar lung tissues with scattered congestion per bronchiolar and perivascular cells, as well as, inflammatory cells were observed. The data suggested that resveratrol exerts its protective effect by modulating the extent of oxidative status and improving the enzymatic/non-enzymatic antioxidant defense system, moreover, decreases the pathological changes in animals against the lung damage caused by nicotine.
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Affiliation(s)
- Reham Z Hamza
- Zoology Department, Faculty of Science, Zagazig University, Zagazig 44519, Egypt.,Biology Department , Faculty of Science , Taif University, Taif 888, Saudi Arabia
| | - Nahla S El-Shenawy
- Zoology Department, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt
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26
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Huang TH, Chen CC, Liu HM, Lee TY, Shieh SH. Resveratrol Pretreatment Attenuates Concanavalin A-induced Hepatitis through Reverse of Aberration in the Immune Response and Regenerative Capacity in Aged Mice. Sci Rep 2017; 7:2705. [PMID: 28578410 PMCID: PMC5457448 DOI: 10.1038/s41598-017-02881-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Accepted: 04/19/2017] [Indexed: 12/22/2022] Open
Abstract
Loss of regenerative capacity plays a critical role in age-related autoimmune hepatitis. Evidence implicates SIRT1 and p66shc in cell senescence, apoptosis, oxidative stress, and proliferation. This study investigated the effect of resveratrol on concanavalin A (Con A)-induced hepatitis in aged mice and the roles of SIRT1 and p66shc. Aged mice were administrated resveratrol (30 mg/kg orally) seven times at an interval of 12 h before a single intravenous injection of Con A (20 mg/kg). Results showed that the cytokines, TNF-α, IL-6, IFN-γ, and MCP-1, as well as infiltration of macrophages, neutrophils, and T lymphocytes in liver were dramatically enhanced in the mice given only Con A. The aged mouse livers showed markedly raised oxidative stress and cell apoptosis. This oxidative stress further aggravated regenerative dysfunction as indicated by the decreased levels of Ki67, PCNA, Cyclin D1, and Cdk2. Conversely, these phenomena were attenuated by pretreatment with resveratrol. Moreover, resveratrol suppressed the elevation of p66shc in the liver by reversing Con-A-mediated downregulation of SIRT1. The findings suggest that resveratrol protected against Con A-induced hepatitis in aged mice by attenuating an aberration of immune response and liver regeneration, partially via the mechanism of SIRT1-mediated repression of p66shc expression.
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Affiliation(s)
- Tse-Hung Huang
- Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan, ROC.,School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan, ROC.,School of Nursing, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan, ROC
| | - Chin-Chang Chen
- School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan, ROC.,Graduate Institute of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan, ROC.,Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan, ROC
| | - Hsuan-Miao Liu
- Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Tzung-Yan Lee
- Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan, ROC. .,School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan, ROC. .,Graduate Institute of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan, ROC.
| | - Sue-Heui Shieh
- Department of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan, ROC.
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27
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Resveratrol protects the loss of connexin 43 induced by ethanol exposure in neonatal mouse cardiomyocytes. Naunyn Schmiedebergs Arch Pharmacol 2017; 390:651-660. [DOI: 10.1007/s00210-017-1368-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Accepted: 03/16/2017] [Indexed: 11/26/2022]
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28
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Chi KK, Zhang WH, Chen Z, Cui Y, He W, Wang SG, Zhang C, Chen J, Wang GC. Comparison of quercetin and resveratrol in the prevention of injury due to testicular torsion/detorsion in rats. Asian J Androl 2017; 18:908-912. [PMID: 26620457 PMCID: PMC5109887 DOI: 10.4103/1008-682x.167720] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Quercetin (QE) and resveratrol (RSV) are powerful antioxidants with the potential to protect the testes against ischemia/reperfusion (I/R) injury. We compared their effects in testicular torsion/detorsion (T/D) in adult rats. Twenty-four male Wistar rats were divided into four groups: sham (group A), T/D (group B), T/D treated with QE (group C), and T/D treated with RSV (group D). QE (20 mg kg−1) and RSV (20 mg kg−1) were injected intra-peritoneally at 60 min of torsion. After 90 min of surgically induced torsion, the testicular cord was restored to its anatomical position. Twenty-four hour after torsion, blood and tissue samples were obtained for further examination. Testicular tissue malondialdehyde (MDA) and nitric oxide (NO) levels and serum total oxidant status (TOS) were higher in group B than in group A (P < 0.05). Group A had higher serum total antioxidant status (TAS) than group B. (P < 0.05) QE and RSV significantly lowered MDA, NO, and TOS levels and TAS consumption (P < 0.05). QE reduced the MDA and TOS levels more than RSV (P < 0.05), but their effects on NO reduction and TAS consumption were similar (P > 0.05). Group A had normal testicular architecture (grade 1). Groups C (mean grade 2.60) and D (mean grade 3.00) had lower testicular injury grades than group B (mean grade 3.45) (P < 0.05). Group C had lower testicular injury grade than group D (P < 0.05). Treatment with QE and RSV protects against I/R injury after testicular T/D. QE may exhibit better function than RSV at the doses tested in this study.
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Affiliation(s)
- Kai-Kai Chi
- Department of Urology, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, Henan, China
| | - Wen-Hui Zhang
- Department of Hematology, Henan Provincial People's Hospital, Zhengzhou 450002, Henan, China
| | - Zhu Chen
- Department of Urology, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, Henan, China
| | - Yong Cui
- Department of Urology, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, Henan, China
| | - Wei He
- Department of Urology, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, Henan, China
| | - Suo-Gang Wang
- Department of Urology, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, Henan, China
| | - Chan Zhang
- Department of Urology, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, Henan, China
| | - Jie Chen
- Department of Urology, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, Henan, China
| | - Guang-Ce Wang
- Department of Urology, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, Henan, China
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29
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Szkudelska K, Deniziak M, Roś P, Gwóźdź K, Szkudelski T. Resveratrol alleviates ethanol-induced hormonal and metabolic disturbances in the rat. Physiol Res 2016; 66:135-145. [PMID: 27782737 DOI: 10.33549/physiolres.933335] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Resveratrol is a polyphenol found in different plant species and having numerous health-promoting properties in animals and humans. However, its protective action against deleterious effects of ethanol is poorly elucidated. In the present study, the influence of resveratrol (10 mg/kg/day) on some hormones and metabolic parameters was determined in rats ingesting 10 % ethanol solution for two weeks. Blood levels of insulin, glucagon and adiponectin were affected by ethanol, however, resveratrol partially ameliorated these changes. Moreover, in ethanol drinking rats, liver lipid accumulation was increased, whereas resveratrol was capable of reducing liver lipid content, probably due to decrease in fatty acid synthesis. Resveratrol decreased also blood levels of triglycerides and free fatty acids and reduced gamma-glutamyl transferase activity in animals ingesting ethanol. These results show that resveratrol, already at low dose, alleviates hormonal and metabolic changes induced by ethanol in the rat and may be useful in preventing and treating some consequences of alcohol consumption.
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Affiliation(s)
- K Szkudelska
- Department of Animal Physiology and Biochemistry, Poznan University of Life Sciences, Poznan, Poland.
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30
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Resveratrol prevents oxidative damage and loss of sperm motility induced by long-term treatment with valproic acid in Wistar rats. ACTA ACUST UNITED AC 2016; 68:435-43. [DOI: 10.1016/j.etp.2016.07.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Revised: 06/13/2016] [Accepted: 07/01/2016] [Indexed: 01/11/2023]
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31
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ZAREI S, SAIDIJAM M, KARIMI J, YADEGARAZARI R, REZAEI FARIMANI A, HOSSEINI-ZIJOUD SS, GOODARZI MT. Effect of resveratrol on resistin and apelin gene expressions in adipose tissue of diabetic rats. Turk J Med Sci 2016; 46:1561-1567. [DOI: 10.3906/sag-1505-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2015] [Accepted: 12/15/2015] [Indexed: 11/03/2022] Open
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32
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Akomolafe SF, Oboh G, Akindahunsi AA, Afolayan AJ. Tetracarpidium conophorum ameliorates oxidative reproductive toxicity induced by ethanol in male rats. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2015; 15:439. [PMID: 26682909 PMCID: PMC4683755 DOI: 10.1186/s12906-015-0960-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Accepted: 12/09/2015] [Indexed: 11/10/2022]
Abstract
Background Tetracarpidium conophorum (Mull. Arg.) Hutch. & Dalz is one of the many medicinal plants used for ages in folklore as male fertility enhancers. The current study evaluates the effect of the plant leaf extract on alcohol - induced reproductive toxicity in male rats. Methods Thirty rats were randomly divided into six groups of five animals each; Group 1 (positive control) received normal saline only; Group 2 (ethanol alone) were given only 30 % ethanol orally at 7 ml/kg body weight per day, thrice in a week; Group 3, 4, 5 were given ethanol and co-treated with 50 mg/kg, 500 mg/kg and 1000 mg/kg body weight of leaf extract respectively while Group 6 were given ethanol and co-treated with a fertility drug, clomiphene citrate. All the drugs were given daily and the experiment lasted for twenty one consecutive days. Results Alcohol ingestion resulted in a significant (p < 0.05) decrease in water, food intake and marked elevation of lipid peroxidation as assessed by the accumulation of malondialdehyde (MDA) in the reproductive tissues. Precisely, MDA level was elevated in the testis, epididymis, seminal vesicle and prostate gland by 81 %, 63 %, 95 % and 91 %, respectively. Furthermore, levels of total protein, reduced glutathione (GSH), vitamin C and activities of antioxidant enzymes in the reproductive tissues were significantly (p < 0.0001) reduced in ethanol-ingested rats. Interestingly, co-administration of T. conophorum with ethanol led to almost complete inhibition of lipid peroxidation thereby enhancing antioxidant status of the reproductive tissues. Conclusion Overall, T. conophorum ameliorates oxidative reproductive toxicity induced by ethanol in male rats and its ameliorative effect comparable well with the fertility drug, clomiphene citrate.
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33
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McGill MR, Du K, Weemhoff JL, Jaeschke H. Critical review of resveratrol in xenobiotic-induced hepatotoxicity. Food Chem Toxicol 2015; 86:309-18. [PMID: 26561740 DOI: 10.1016/j.fct.2015.11.003] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2015] [Revised: 10/30/2015] [Accepted: 11/02/2015] [Indexed: 02/07/2023]
Abstract
Use of natural products is increasingly popular. In fact, many patients with liver diseases self-medicate with herbal supplements. Resveratrol (RSV), in particular, is a common natural product that can reduce injury in experimental models of liver disease. Xenobiotic hepatotoxicity is a particularly important area-of-need for therapeutics. Drug-induced liver injury, for example, is the most common cause of acute liver failure (ALF) and ALF-induced deaths in many countries. Importantly, RSV protects against hepatotoxicity in animal models in vivo caused by several drugs and chemicals and may be an effective intervention. Although many mechanisms have been proposed to explain the protection, not all are consistent with other data. Furthermore, RSV suffers from other issues, including limited bioavailability due to extensive hepatic metabolism. The purpose of this article is to summarize recent findings on the protective effects of RSV in xenobiotic-induced liver injury and other forms of liver injury and to provide a critical review of the underlying mechanisms. New mechanisms that are more consistent with data emerging from the toxicology field are suggested. Efforts to move RSV into clinical use are also considered. Overall, RSV is a promising candidate for therapeutic use, but additional studies are needed to better understand its effects.
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Affiliation(s)
- Mitchell R McGill
- Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA.
| | - Kuo Du
- Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA
| | - James L Weemhoff
- Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA
| | - Hartmut Jaeschke
- Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA
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34
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Zhang H, Sun Q, Xu T, Hong L, Fu R, Wu J, Ding J. Resveratrol attenuates the progress of liver fibrosis via the Akt/nuclear factor-κB pathways. Mol Med Rep 2015; 13:224-30. [PMID: 26530037 DOI: 10.3892/mmr.2015.4497] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2014] [Accepted: 09/01/2015] [Indexed: 11/06/2022] Open
Abstract
Liver fibrosis is a wound-healing response to chronic liver injury that results in the accumulation of extracellular matrix proteins. It eventually leads to cirrhosis of the liver and liver failure, and it is a critical threat to the health and lives of patients with chronic liver diseases. No effective treatment is currently available. Resveratrol is a polyphenol with antioxidant, anti‑cancer and anti‑inflammatory properties. It has been reported that resveratrol prevents liver fibrosis, possibly by inhibiting NF‑κB activation. The present study investigated the mechanisms by which resveratrol prevented liver fibrosis, focusing on the possible involvement of the NF‑κB pathway. Mice with carbon tetrachloride (CCl4)‑induced liver fibrosis were treated with various concentrations of resveratrol. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and tumor necrosis factor (TNF)‑α were detected by ELISAs. Expression of α‑smooth muscle actin (α‑SMA), collagen I, inhibitor of NF‑κB (IκB) and NF‑κB were detected by western blot analysis. In addition, the present study examined the effects of resveratrol on the expression of fibrosis markers in LX‑2 cells. Western blot analysis was further used to detect the levels of Akt and phosphorylated Akt, as well as the nuclear levels of IκB, phosphorylated IκB and NF‑κB p65. The expression of α‑SMA in resveratrol‑treated LX‑2 cells was detected by immunofluorescence and flow cytometry, which demonstrated that resveratrol decreased the expression of α‑SMA in LX‑2 cells. Resveratrol also decreased CCl4‑induced upregulation of serum AST, ALT, TNF‑α, α‑SMA and collagen I. Finally, resveratrol prevented the activation of NF‑κB and Akt. The results of the present study therefore indicated that resveratrol attenuates liver fibrosis via the Akt/NF-κB pathways.
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Affiliation(s)
- Hui Zhang
- Department of Infectious Diseases, The Third Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325200, P.R. China
| | - Qingfeng Sun
- Department of Infectious Diseases, The Third Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325200, P.R. China
| | - Tingyan Xu
- Department of Infectious Diseases, The Third Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325200, P.R. China
| | - Liang Hong
- Department of Infectious Diseases, The Third Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325200, P.R. China
| | - Rongquan Fu
- Department of Infectious Diseases, The Third Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325200, P.R. China
| | - Jinguo Wu
- Department of Infectious Diseases, The Third Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325200, P.R. China
| | - Jiguang Ding
- Department of Infectious Diseases, The Third Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325200, P.R. China
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Silva P, Fernandes E, Carvalho F. Dual effect of red wine on liver redox status: a concise and mechanistic review. Arch Toxicol 2015; 89:1681-1693. [PMID: 26026610 DOI: 10.1007/s00204-015-1538-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2015] [Accepted: 05/12/2015] [Indexed: 01/09/2023]
Abstract
Chronic ethanol consumption is a strong risk factor for the development of liver disease. Multiple mechanisms are involved in ethanol-mediated liver injury; oxidative stress being pointed has an important factor. However, it should be noted that moderate consumption of red wine has been associated with hepatoprotective effects, mainly due to the antioxidant effect of resveratrol, one of its polyphenolic compounds. In this paper, the potential molecular mechanisms through which the protective effects of resveratrol counteract the oxidative effect of ethanol and the way as this dual effect impacts liver oxidative stress are reviewed. Mechanistic evaluation of modulation of oxidative signaling pathways by ethanol and resveratrol may explain the pathogenesis of various liver diseases and ultimately to disclose possible pharmacological therapies.
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Affiliation(s)
- Paula Silva
- UCIBIO-REQUIMTE, Laboratory of Histology and Embryology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira no. 228, 4050-313, Porto, Portugal.
| | - Eduarda Fernandes
- UCIBIO-REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
| | - Félix Carvalho
- UCIBIO-REQUIMTE, Department of Biological Sciences, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira no. 228, 4050-313, Porto, Portugal.
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36
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Casas-Grajales S, Muriel P. Antioxidants in liver health. World J Gastrointest Pharmacol Ther 2015; 6:59-72. [PMID: 26261734 PMCID: PMC4526841 DOI: 10.4292/wjgpt.v6.i3.59] [Citation(s) in RCA: 75] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2015] [Revised: 06/04/2015] [Accepted: 06/18/2015] [Indexed: 02/06/2023] Open
Abstract
Liver diseases are a worldwide medical problem because the liver is the principal detoxifying organ and maintains metabolic homeostasis. The liver metabolizes various compounds that produce free radicals (FR). However, antioxidants scavenge FR and maintain the oxidative/antioxidative balance in the liver. When the liver oxidative/antioxidative balance is disrupted, the state is termed oxidative stress. Oxidative stress leads to deleterious processes in the liver and produces liver diseases. Therefore, restoring antioxidants is essential to maintain homeostasis. One method of restoring antioxidants is to consume natural compounds with antioxidant capacity. The objective of this review is to provide information pertaining to various antioxidants found in food that have demonstrated utility in improving liver diseases.
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37
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Zhou Y, Chen K, He L, Xia Y, Dai W, Wang F, Li J, Li S, Liu T, Zheng Y, Wang J, Lu W, Yin Q, Zhou Y, Lu J, Teng H, Guo C. The Protective Effect of Resveratrol on Concanavalin-A-Induced Acute Hepatic Injury in Mice. Gastroenterol Res Pract 2015; 2015:506390. [PMID: 26089871 PMCID: PMC4458299 DOI: 10.1155/2015/506390] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2014] [Revised: 04/01/2015] [Accepted: 05/02/2015] [Indexed: 12/29/2022] Open
Abstract
Pharmacologic Relevance. Resveratrol, an antioxidant derived from grapes, has been reported to modulate the inflammatory process. In this study, we investigated the effects of resveratrol and its mechanism of protection on concanavalin-A- (ConA-) induced liver injury in mice. Materials and Methods. Acute autoimmune hepatitis was induced by ConA (20 mg/kg) in Balb/C mice; mice were treated with resveratrol (10, 20, and 30 mg/kg) daily by oral gavage for fourteen days prior to a single intravenous injection of ConA. Eight hours after injection, histologic grading, proinflammatory cytokine levels, and hedgehog pathway activity were determined. Results. After ConA injection, the cytokines IL-2, IL-6, and TNF-α were increased, and Sonic hedgehog (Shh), Glioblastoma- (Gli-) 1, and Patched (Ptc) levels significantly increased. Pretreatment with resveratrol ameliorated the pathologic effects of ConA-induced autoimmune hepatitis and significantly inhibited IL-2, IL-6, TNF-α, Shh, Gli-1, and Ptc. The effects of resveratrol on the hedgehog pathway were studied by western blotting and immunohistochemistry. Resveratrol decreased Shh expression, possibly by inhibiting Shh expression in order to reduce Gli-1 and Ptc expression. Conclusion. Resveratrol protects against ConA-induced autoimmune hepatitis by decreasing cytokines expression in mice. The decreases seen in Gli-1 and Ptc may correlate with the amelioration of hedgehog pathway activity.
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Affiliation(s)
- Yingqun Zhou
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Kan Chen
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Lei He
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Yujing Xia
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Weiqi Dai
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Fan Wang
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Jingjing Li
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Sainan Li
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Tong Liu
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Yuanyuan Zheng
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Jianrong Wang
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
- The First Clinical Medical College of Nanjing Medical University, Nanjing 210029, China
| | - Wenxia Lu
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
- The First Clinical Medical College of Nanjing Medical University, Nanjing 210029, China
| | - Qin Yin
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
- The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Yuqing Zhou
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
- The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Jie Lu
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Hongfei Teng
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
- Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Chuanyong Guo
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
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Madrigal-Santillán E, Madrigal-Bujaidar E, Álvarez-González I, Sumaya-Martínez MT, Gutiérrez-Salinas J, Bautista M, Morales-González &A, González-Rubio MGLY, Aguilar-Faisal JL, Morales-González JA. Review of natural products with hepatoprotective effects. World J Gastroenterol 2014; 20:14787-14804. [PMID: 25356040 PMCID: PMC4209543 DOI: 10.3748/wjg.v20.i40.14787] [Citation(s) in RCA: 220] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2013] [Revised: 12/11/2013] [Accepted: 04/21/2014] [Indexed: 02/06/2023] Open
Abstract
The liver is one of the most important organs in the body, performing a fundamental role in the regulation of diverse processes, among which the metabolism, secretion, storage, and detoxification of endogenous and exogenous substances are prominent. Due to these functions, hepatic diseases continue to be among the main threats to public health, and they remain problems throughout the world. Despite enormous advances in modern medicine, there are no completely effective drugs that stimulate hepatic function, that offer complete protection of the organ, or that help to regenerate hepatic cells. Thus, it is necessary to identify pharmaceutical alternatives for the treatment of liver diseases, with the aim of these alternatives being more effective and less toxic. The use of some plants and the consumption of different fruits have played basic roles in human health care, and diverse scientific investigations have indicated that, in those plants and fruits so identified, their beneficial effects can be attributed to the presence of chemical compounds that are called phytochemicals. The present review had as its objective the collecting of data based on research conducted into some fruits (grapefruit, cranberries, and grapes) and plants [cactus pear (nopal) and cactus pear fruit, chamomile, silymarin, and spirulina], which are consumed frequently by humans and which have demonstrated hepatoprotective capacity, as well as an analysis of a resin (propolis) and some phytochemicals extracted from fruits, plants, yeasts, and algae, which have been evaluated in different models of hepatotoxicity.
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Ahmad A, Ahmad R. Resveratrol mitigate structural changes and hepatic stellate cell activation in N'-nitrosodimethylamine-induced liver fibrosis via restraining oxidative damage. Chem Biol Interact 2014; 221:1-12. [PMID: 25064540 DOI: 10.1016/j.cbi.2014.07.007] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2014] [Revised: 06/13/2014] [Accepted: 07/16/2014] [Indexed: 01/30/2023]
Abstract
Resveratrol, a polyphenol, found in skin of red grapes, peanuts and berries possesses anti-inflammatory, anti-carcinogenic and lipid modulation properties. Here, we demonstrate in vivo antifibrotic activity of resveratrol in a mammalian model, wherein hepatic fibrosis was induced by N'-nitrosodimethylamine (NDMA) administration. Apart from being a potent hepatotoxin, NDMA is a known mutagen and carcinogen, as well. To induce hepatic fibrosis, rats were administered NDMA (i.p.) in 10mg/kgb.wt thrice/week for 21 days. Another group of animals received resveratrol supplement (10mg/kgb.wt) subsequent to NDMA administration and were sacrificed weekly. The changes in selected biomarkers were monitored to compare profibrotic effects of NDMA and antifibrotic activity of resveratrol. The selected biomarkers were: sera transaminases, ALP, bilirubin, liver glycogen, LPO, SOD, protein carbonyl content, ATPases (Ca(2+), Mg(2+), Na(+)/K(+)) and hydroxyproline/collagen content. Alterations in liver architecture were assessed by H&E, Masson's trichrome and reticulin staining of liver biopsies. Immuno-histochemistry and immunoblotting were employed to examine expression of α-SMA. Our results demonstrate that during NDMA-induced liver fibrosis transaminases, ALP, bilirubin, hydroxyproline and liver collagen increases, while liver glycogen is depleted. The decline in SOD (>65%) and ATPases, which were concomitant with the elevation in MDA and protein carbonyls, strongly indicate oxidative damage. Fibrotic transformation of liver in NDMA-treated rats was verified by histopathology, immuno-histochemistry and immunoblotting data, with the higher expressivity of α-SMA-positive HSCs being most established diagnostic immuno-histochemical marker of HSCs. Resveratrol-supplement refurbished liver architecture by significantly restoring levels of biomarkers of oxidative damage (MDA, SOD, protein carbonyls and membrane-bound ATPases). Therefore, we conclude that antifibrotic effect of resveratrol is due to restrained oxidative damage and down-regulation of α-SMA, which inhibits HSC activation to obstruct liver fibrosis.
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Affiliation(s)
- Areeba Ahmad
- Biochemical and Clinical Genetics Laboratory, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, U.P., India
| | - Riaz Ahmad
- Biochemical and Clinical Genetics Laboratory, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, U.P., India.
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Şen E, Tunali Y, Erkan M. Testicular development of male mice offsprings exposed to acrylamide and alcohol during the gestation and lactation period. Hum Exp Toxicol 2014; 34:401-14. [DOI: 10.1177/0960327114542883] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Acrylamide (Ac) in the foods and alcohol (Al) in the drinks are unavoidable. Several previous studies demonstrated that these substances which are taken into the body via diet may cause adverse effects in the cells. However, there is no study about how Ac and Al may affect the male reproductive system of the offspring when consumed by the mother during pregnancy and lactation. For this purpose, sexual development in male mice was evaluated after intake of 14 mg/kg Ac and 2 g/kg Al from gestation day 6 to postnatal day (PND) 21. The weight of the offspring was reduced at birth and PND 21 for those exposed to Ac and/or Al. The gonadosomatic index of male offsprings was reduced except for the Ac-treated lactation group. Both substances induced multinuclear giant cells, degenerative cells, atrophic tubules, and maturation-arrested tubules, while decreased Leydig, Sertoli, and spermatogenic cell numbers. Lipid peroxidation level and superoxide dismutase enzyme activity increased in both Al-treated and Ac and Al-treated groups. There was only reduction in the catalase activity during the gestation and lactation periods. These findings suggest that consumption of Ac together with Al may induce impairments on testicular spermatogenesis in male offsprings.
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Affiliation(s)
- E Şen
- Department of Biology, Faculty of Science, Istanbul University, Vezneciler, Istanbul, Turkey
| | - Y Tunali
- Department of Biology, Faculty of Science, Istanbul University, Vezneciler, Istanbul, Turkey
| | - M Erkan
- Department of Biology, Faculty of Science, Istanbul University, Vezneciler, Istanbul, Turkey
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Akindele AJ, Iyamu EA, Dutt P, Satti NK, Adeyemi OO. Ameliorative Effect of Hydroethanolic Leaf Extract of Byrsocarpus coccineus in Alcohol- and Sucrose-Induced Hypertension in Rats. J Tradit Complement Med 2014; 4:177-88. [PMID: 25161923 PMCID: PMC4142456 DOI: 10.4103/2225-4110.129562] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Hypertension remains a major health problem worldwide considering the prevalence of morbidity and mortality. Plants remain a reliable source of efficacious and better tolerated drugs and botanicals. This study was designed to investigate the effect of the chemo-profiled hydroethanolic leaf extract of Byrsocarpus coccineus in ethanol- and sucrose-induced hypertension. Groups of rats were treated orally (p.o.) with distilled water (10 ml/kg), ethanol (35%; 3 g/kg), sucrose (5-7%), and B. coccineus (100, 200, and 400 mg/kg), and nifedipine together with ethanol and sucrose separately for 8 weeks. At the end of the treatment period, blood pressure and heart rate of rats were determined. Blood was collected for serum biochemical parameters and lipid profile assessment, and the liver, aorta, kidney, and heart were harvested for estimation of in vivo antioxidants and malondialdehyde (MDA). Results obtained in this study showed that B. coccineus at the various doses administered reduced the systolic, diastolic, and arterial blood pressure elevated by ethanol and sucrose. Also, the extract reversed the reduction in catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), and superoxide dismutase (SOD) induced by ethanol and sucrose. The level of MDA was reduced compared to the ethanol- and sucrose-induced hypertensive group. With respect to lipid profile, administration of B. coccineus at the various doses reduced the levels of triglycerides, low-density lipoprotein (LDL), cholesterol, and atherogenic indices, compared to the ethanol and sucrose groups. In conclusion the hydroethanolic leaf extract of B. coccineus exerted significant antihypertensive effect and this is probably related to the antioxidant property and improvement of lipid profile observed in this study.
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Affiliation(s)
- Abidemi J. Akindele
- Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, P. M. B. 12003 Lagos, Nigeria
| | - Endurance A. Iyamu
- Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, P. M. B. 12003 Lagos, Nigeria
| | - Prabhu Dutt
- Natural Products Chemistry (Plants) Division, Indian Institute of Integrative Medicine (Council of Scientific and Industrial Research), Canal Road, Jammu - 180001, India
| | - Naresh K. Satti
- Natural Products Chemistry (Plants) Division, Indian Institute of Integrative Medicine (Council of Scientific and Industrial Research), Canal Road, Jammu - 180001, India
| | - Olufunmilayo O. Adeyemi
- Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, P. M. B. 12003 Lagos, Nigeria
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Aguirre L, Portillo MP, Hijona E, Bujanda L. Effects of resveratrol and other polyphenols in hepatic steatosis. World J Gastroenterol 2014; 20:7366-7380. [PMID: 24966607 PMCID: PMC4064082 DOI: 10.3748/wjg.v20.i23.7366] [Citation(s) in RCA: 93] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2013] [Revised: 12/04/2013] [Accepted: 01/19/2014] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease covers a wide spectrum of liver pathologies which range from simple steatosis to non-alcoholic steatohepatitis. Polyphenols are members of a very large family of plant-derived compounds that can have beneficial effects on human health, and thus their study has become an increasingly important area of human nutrition research. The aim of the present review is to compile published data concerning the effects of both isolated polyphenols as well as polyphenol extracts, on hepatocyte and liver fat accumulation under different steatosis-inducing conditions. The results reported clearly show that this group of biomolecules is able to reduce fat accumulation, but further studies are needed to establish the optimal dose and treatment period length. With regard to the potential mechanisms of action, there is a good consensus. The anti-lipidogenic effect of polyphenols is mainly due to reduced fatty acid and triacylglycerol synthesis, increased in fatty acid oxidation, and reduced of oxidative stress and inflammation. As a general conclusion, it can be stated that polyphenols are biomolecules which produce hepatoprotective effects. To date, these beneficial effects have been demonstrated in cultured cells and animal models. Thus, studies performed in humans are needed before these molecules can be considered as truly useful tools in the prevention of liver steatosis.
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Liu H, Qi X, Cao S, Li P. Protective effect of flavonoid extract from Chinese bayberry (Myrica rubra Sieb. et Zucc.) fruit on alcoholic liver oxidative injury in mice. J Nat Med 2014; 68:521-9. [DOI: 10.1007/s11418-014-0829-9] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2013] [Accepted: 02/22/2014] [Indexed: 12/27/2022]
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Collins MA, Tajuddin N, Moon KH, Kim HY, Nixon K, Neafsey EJ. Alcohol, phospholipase A2-associated neuroinflammation, and ω3 docosahexaenoic acid protection. Mol Neurobiol 2014; 50:239-45. [PMID: 24705861 DOI: 10.1007/s12035-014-8690-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2013] [Accepted: 03/24/2014] [Indexed: 01/03/2023]
Abstract
Chronic alcohol (ethanol) abuse causes neuroinflammation and brain damage that can give rise to alcoholic dementia. Insightfully, Dr. Albert Sun was an early proponent of oxidative stress as a key factor in alcoholism-related brain deterioration. In fact, oxidative stress has proven to be critical to the hippocampal and temporal cortical neurodamage resulting from repetitive "binge" alcohol exposure in adult rat models. Although the underlying mechanisms are uncertain, our immunoelectrophoretic and related assays in binge alcohol experiments in vivo (adult male rats) and in vitro (rat organotypic hippocampal-entorhinal cortical slice cultures) have implicated phospholipase A(2) (PLA(2))-activated neuroinflammatory pathways, release of pro-oxidative arachidonic acid (20:4 ω6), and elevated oxidative stress adducts (i.e., 4-hydroxynonenal-protein adducts). Also, significantly increased by the binge alcohol treatments was aquaporin-4 (AQP4), a water channel enriched in astrocytes that, when augmented, may trigger brain (esp. cellular) edema and neuroinflammation; of relevance, glial swelling is known to provoke increased PLA(2) activities or levels. Concomitant with PLA(2) activation, the results have further implicated binge alcohol-elevated poly (ADP-ribose) polymerase-1 (PARP-1), an oxidative stress-responsive DNA repair enzyme linked to parthanatos, a necrotic-like neuronal death process. Importantly, supplementation of the brain slice cultures with docosahexaenoic acid (22:6 ω3) exerted potent suppression of the induced changes in PLA(2) isoforms, AQP4, PARP-1 and oxidative stress footprints, and prevention of the binge alcohol neurotoxicity, by as yet unknown mechanisms. These neuroinflammatory findings from our binge alcohol studies and supportive rat binge studies in the literature are reviewed.
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Affiliation(s)
- Michael A Collins
- Department of Molecular Pharmacology & Therapeutics, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, 60153, USA,
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Yuluğ E, Türedi S, Karagüzel E, Kutlu O, Menteşe A, Alver A. The short term effects of resveratrol on ischemia-reperfusion injury in rat testis. J Pediatr Surg 2014; 49:484-9. [PMID: 24650483 DOI: 10.1016/j.jpedsurg.2013.08.028] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2013] [Revised: 07/15/2013] [Accepted: 08/19/2013] [Indexed: 12/12/2022]
Abstract
PURPOSE The purpose of this study was to identify changes taking place in the rat testis at the 24th hour of reperfusion following testicular torsion and to evaluate the effects of resveratrol (RSV), a powerful antioxidant, in preventing these changes using novel biochemical parameters and histopathology. METHODS Eighteen adult male rats were divided into three groups: Sham-operated (S), torsion/detorsion (T/D), and T/D+RSV groups. In the T/D group, testicular ischemia was achieved by rotating the left testis 720° clockwise for 4h. In the T/D+RSV group, 20mg/kg RSV was administered intraperitoneally 30 min before detorsion. All rats were sacrificed 24h after detorsion. Serum and tissue malondialdehyde (MDA) concentrations, ischemia modified albumin (IMA), total oxidative status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and histopathological damage score were analyzed. RESULTS Serum MDA, IMA, TOS, and OSI levels rose significantly in the T/D group. Serum MDA and IMA values were lower in the T/D+RES groups, but not significantly. OSI and TOS values were lower in the T/D+RES group, and the difference was significant. TAS values decreased significantly in the T/D group and rose in the T/D+RSV group, but not significantly. Ipsilateral tissue MDA values were significantly elevated in the T/D group and decreased in the T/D+RSV group, but not significantly. Apoptosis and histopathological damage increased significantly in the T/D group and decreased significantly in the T/D+RSV group. In the contralateral testis, apoptosis increased significantly in the T/D group. It decreased significantly in the T/D+RSV group. CONCLUSIONS Our findings show that RSV had a protective effect against oxidative damage induced with a testicular T/D model, especially at the antiapoptotic and histopathological level. OSI may be a good guide to the clinical status of testicular T/D.
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Affiliation(s)
- Esin Yuluğ
- Department of Histology and Embryology, Karadeniz Technical University, Faculty of Medicine, 61080, Trabzon, Turkey.
| | - Sibel Türedi
- Department of Histology and Embryology, Karadeniz Technical University, Faculty of Medicine, 61080, Trabzon, Turkey
| | - Ersagun Karagüzel
- Department of Urology, Karadeniz Technical University, Faculty of Medicine, 61080, Trabzon, Turkey
| | - Omer Kutlu
- Department of Urology, Karadeniz Technical University, Faculty of Medicine, 61080, Trabzon, Turkey
| | - Ahmet Menteşe
- Program of Medical Laboratory Techniques, Vocational School of Health Sciences, Karadeniz Technical University, 61080, Trabzon, Turkey; Department of Medical Biochemistry, Karadeniz Technical University, Faculty of Medicine, 61080, Trabzon, Turkey
| | - Ahmet Alver
- Department of Medical Biochemistry, Karadeniz Technical University, Faculty of Medicine, 61080, Trabzon, Turkey
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Han C, Wan H, Ma S, Liu D, He F, Wang J, Pan Z, Liu H, Li L, He H, Xu H, Wei S, Xu F. RETRACTED: Role of mammalian sirtuin 1 (SIRT1) in lipids metabolism and cell proliferation of goose primary hepatocytes. Mol Cell Endocrinol 2014; 382:282-291. [PMID: 24145124 DOI: 10.1016/j.mce.2013.10.012] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2013] [Revised: 10/07/2013] [Accepted: 10/11/2013] [Indexed: 12/17/2022]
Abstract
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Authors. It has come to the attention of the corresponding author that there are two errors in Section 3.1 of the Results section titled “Effect of overfeeding on gene expression and enzyme activity of several genes in liver”. The first error is that the article contains the wrong number of overfeeding days. The second error is that there are incorrect correlations between liver weight, lipids content in live and plasma metabolic substrates because of the wrong overfeeding days. The authors take responsibility for them and apologize to the readership of Molecular and Cellular Endocrinology.
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Affiliation(s)
- Chunchun Han
- Institute of Animal Breeding & Genetic, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China.
| | - Huofu Wan
- Institute of Animal Breeding & Genetic, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China
| | - Shuang Ma
- College of Life Sciences, University of Chinese Academy of Science, Beijing 100049, PR China
| | - Dandan Liu
- Institute of Animal Breeding & Genetic, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China
| | - Fang He
- Institute of Animal Breeding & Genetic, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China
| | - Jiwen Wang
- Institute of Animal Breeding & Genetic, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China
| | - Zhixiong Pan
- Institute of Animal Breeding & Genetic, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China
| | - Hehe Liu
- Institute of Animal Breeding & Genetic, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China
| | - Liang Li
- Institute of Animal Breeding & Genetic, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China
| | - Hua He
- Institute of Animal Breeding & Genetic, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China
| | - Hongyong Xu
- Institute of Animal Breeding & Genetic, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China
| | - Shouhai Wei
- Institute of Animal Breeding & Genetic, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China
| | - Feng Xu
- Institute of Animal Breeding & Genetic, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China
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The effect of di-n-butyl phthalate on testis and the potential protective effects of resveratrol. Toxicol Ind Health 2013; 32:777-90. [DOI: 10.1177/0748233713512364] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
This study aimed to observe the possible protective effects of resveratrol (RSV) against the damage of di- n-butyl phthalate (DBP) on the testis. The study was conducted in 6 groups of rats with 6 animals in each group aged 20 days. The groups include group 1: control group; group 2: solvent (carboxymethylcellulose (CMC), 10 ml/kg); group 3: 500 mg/kg/day DBP; group 4: 500 mg/kg/day DBP + 20 mg/kg/day RSV; group 5: 1000 mg/kg/day DBP; and group 6: 1000 mg/kg/day DBP + 20 mg/kg/day RSV. Groups were treated by gavage for 30 days. Indirect immunohistochemical staining was performed with c-kit, AT1, and ER-α antibodies. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate–biotin nick-end labeling (TUNEL) method was used for apoptosis. It was found in the DBP-applied groups the C-kit immunostaining, which is parallel to increasing dose, decreased in comparison with the control. C-kit reactivity was similar to that of the control group in the group applied with 500 mg/kg/day + RSV; however, the reactivity was not same in the 1000 mg/kg/day DBP-applied group. It was observed that the reactivity of AT1 increased in the DBP-applied groups. RSV reversed these changes with its protective effects. While there was not much difference between the groups in terms of estrogen receptor reactivity, it was observed that the high dose of DBP reduced the level of estrogen receptor and the resveratrol was not at enough levels in all doses. In TUNEL analysis, high doses of DBP increased the apoptosis in all types of cells; nevertheless, the resveratrol application decreased the apoptosis in the low-level DBP dose. In the statistical analysis, while the length of epithelium and the diameter of seminiferous tubules decreased for all the other groups, it reverted to its original state in the RSV-applied groups. In conclusion, DBP (with increasing dose) administration caused cycle and hormonal changes in testis, resveratrol were recovered the cyclic changes but in hormonal changes, RSV is efficient too but inadequate.
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Liu LQ, Fan ZQ, Tang YF, Ke ZJ. The resveratrol attenuates ethanol-induced hepatocyte apoptosis via inhibiting ER-related caspase-12 activation and PDE activity in vitro. Alcohol Clin Exp Res 2013; 38:683-93. [PMID: 24224909 DOI: 10.1111/acer.12311] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2013] [Accepted: 09/16/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Endoplasmic reticulum (ER) stress plays a key role in cell apoptosis pathways. Caspase-12, a proapoptotic gene induced by ER stress, is also the key molecule in ER-related apoptosis. The purpose of this study is to evaluate the protective activity and possible mechanism of resveratrol (ResV) against ethanol (EtOH)-induced apoptosis in human hepatocyte Chang cell line. METHODS The human hepatocyte Chang cell line was used to test the hypothesis that ResV may alleviate the liver cell apoptosis induced by EtOH. ER stress-inducible proteins and silent mating type information regulation 2 homolog 1 (SIRT1) were assayed by Western blot. Cell viability was studied by MTT assay and apoptosis was measured by Annexin-V and propidium iodide assay. Caspase-12 activation was examined by immunofluorescence staining. Alcohol dehydrogenase-2 (ADH-2) and aldehyde dehydrogenase-2 (ALDH-2) were measured by polymerase chain reaction amplified product length polymorphism. Phosphodiesterase (PDE) activity was assayed in cell lysates using a cyclic nucleotide PDE assay. RESULTS EtOH exposure significantly increased the expression of ER stress markers and activated signaling pathways associated with ER stress. These include GRP78, p-IRE1α, p-eIF2α, p-PERK, ATF4 as well as cleaved caspase-3/12, CHOP/GADD153, and Bax in human hepatocyte Chang cell line. The expression of these proteins were significantly down-regulated by ResV (10 μM) in a SIRT1-dependent manner. ResV can inhibit EtOH-, tunicamycin-, thapsigargin-induced caspase-12 activation. ADH-2 and ALDH-2 activities are lower in this cell line. PDE activity increased by EtOH was inhibited by ResV (10 μM). CONCLUSIONS The results indicate that (i) EtOH-induced activation of caspase-12 could be one of the underlying mechanisms of hepatocyte apoptosis; (ii) EtOH-induced cell apoptosis was alleviated via ResV (10 μM) by inhibiting ER stress and caspase-12 activation in a SIRT1-dependent manner; and (iii) SIRT1 activated indirectly by ResV (10 μM) attenuates EtOH-induced hepatocyte apoptosis partly through inhibiting PDE activity.
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Affiliation(s)
- L Q Liu
- Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
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Pollack RM, Crandall JP. Resveratrol: therapeutic potential for improving cardiometabolic health. Am J Hypertens 2013; 26:1260-8. [PMID: 24025725 DOI: 10.1093/ajh/hpt165] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Resveratrol, a natural polyphenol, has gained attention in recent years because of its connection with the health benefits of red wine and its anticancer activity in vitro. Studies in animal models have demonstrated beneficial effects on glucose metabolism, vascular function and anti-inflammatory and antioxidant properties. Human studies designed to understand the role of resveratrol in the prevention and treatment of age-related conditions such as diabetes, heart disease, and cancer have recently been undertaken. METHODS We searched PubMed for original articles that reported studies of resveratrol in humans, using search terms, including resveratrol, human studies, glucose metabolism, vascular function, and inflammation. We also searched the reference lists of identified articles for additional papers and sought expert opinion on relevant studies. RESULTS Resveratrol treatment has shown beneficial effects on glucose and lipid metabolism in some, but not all studies. Study population, resveratrol source, and dose have varied widely, potentially explaining inconsistent findings. Improvements were noted in endothelial function, systolic blood pressure, and markers of oxidative stress and inflammation in several studies. CONCLUSIONS Despite the strong preclinical evidence of positive cardiometabolic effects, studies to date have not confirmed resveratrol's benefit in humans. Study variability and methodological issues limit interpretation of available results. Additional research, focusing on subjects with defined metabolic defects and using a range of doses, is needed to advance the field.
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Affiliation(s)
- Rena M Pollack
- Division of Endocrinology, Diabetes Research Center, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, New York
| | - Jill P Crandall
- Division of Endocrinology, Diabetes Research Center, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, New York.
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Denek Z, Erbil G, Ozbal S, Micili SC, Ozogul C. The effects of resveratrol against trifluralin toxicity in the urinary tract of rats. Toxicol Ind Health 2013; 32:106-17. [DOI: 10.1177/0748233713498437] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The herbicide itself and the degradation products are highly toxic on biological systems. The aim of this study is to investigate the potential toxic effects of trifluralin (TRF) on the urinary system of male rats and to investigate the protective effects of resveratrol (RSV) in TRF-induced urinary system damage. A total of 35 male Wistar rats were randomly divided into: (1) control group, (2) sham group, (3) low dose TRF group (0.8 g/kg/day), (4) high dose TRF group (2 g/kg/day) and (5) high dose TRF + RSV group 10 mg/kg/day. RSV was administered for 21 days by intragastric gavage at a dose of 10 mg/kg/day after induction of TRF. Kidney, ureter and urinary bladder tissue was examined using light microscopy and ultrastructurally. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling was performed to detect apoptosis. Superoxide dismutase (SOD), glutathion peroxidase (GPx) and malondialdehyde (MDA) levels were also evaluated biochemically for oxidative stress parameters. Histological evaluation showed that TRF increases apoptosis and oxidative stress, causes histological tissue damages and biochemical changes in the kidneys but does not cause any damage to the ureter and bladder. Treatment with RSV significantly attenuated tissue damage in the urinary system of rats. Apopitotic cells were significantly decreased in the treatment group. Additionally, treatment with RSV decreased SOD and GPx levels and increased MDA levels in the kidney tissue of animals subjected to TRF. These results show that RSV can significantly minimize histological damage and biochemical differences in treating TRF-induced kidney injury in rats.
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Affiliation(s)
- Ziya Denek
- Department of Histology and Embryology, School of Medicine, Dokuz Eylul University, Inciralti, Izmir, Turkey
| | - Guven Erbil
- Department of Histology and Embryology, School of Medicine, Dokuz Eylul University, Inciralti, Izmir, Turkey
| | - Seda Ozbal
- Department of Histology and Embryology, School of Medicine, Dokuz Eylul University, Inciralti, Izmir, Turkey
| | - Serap Cilaker Micili
- Department of Histology and Embryology, School of Medicine, Dokuz Eylul University, Inciralti, Izmir, Turkey
| | - Candan Ozogul
- Department of Histology and Embryology, School of Medicine, Gazi University, Ankara, Turkey
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