|
1
|
Abdi M, Fadaee M, Jourabchi A, Karimzadeh H, Kazemi T. Cyclophosphamide-Induced Infertility and the Impact of Antioxidants. Am J Reprod Immunol 2024; 92:e70014. [PMID: 39625043 DOI: 10.1111/aji.70014] [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: 08/20/2024] [Revised: 10/15/2024] [Accepted: 10/24/2024] [Indexed: 12/07/2024] Open
Abstract
An important drawback of anticancer chemotherapy is the harm it causes to healthy cells. Cyclophosphamide (CP) is a widely used chemotherapeutic alkylating agent that is regularly used in cancer treatment. However, it can cause severe side effects, including genotoxicity, due to its ability to damage DNA. This toxicity is thought to be associated with oxidative stress induced by an excessive amount of reactive oxygen species (ROS). Therefore, there is a specific focus on the potential effects of anticancer treatments on fertility. Due to the increasing life expectancy of cancer patients, those desiring parenthood may face the negative impacts of therapies. Utilizing substances with antioxidant and cytoprotective characteristics to protect the reproductive system from harmful consequences during chemotherapy would be highly beneficial. This review introduces the physiological and pathological roles of ROS in the reproductive systems of both males and females, then we address the adverse effects of CP administration on infertility and discuss how antioxidants can reverse these effects.
Collapse
Affiliation(s)
- Morteza Abdi
- Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Manouchehr Fadaee
- Student Research Committee, Tabriz University of Medical Science, Tabriz, Iran
- Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amirreza Jourabchi
- Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hadi Karimzadeh
- Student Research Committee, Tabriz University of Medical Science, Tabriz, Iran
| | - Tohid Kazemi
- Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Immunology Research Center, Tabriz University of Medical Science, Tabriz, Iran
| |
Collapse
|
|
2
|
Wei Y, Jia S, Ding Y, Xia S, Giunta S. Balanced basal-levels of ROS (redox-biology), and very-low-levels of pro-inflammatory cytokines (cold-inflammaging), as signaling molecules can prevent or slow-down overt-inflammaging, and the aging-associated decline of adaptive-homeostasis. Exp Gerontol 2023; 172:112067. [PMID: 36535453 DOI: 10.1016/j.exger.2022.112067] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 12/11/2022] [Accepted: 12/15/2022] [Indexed: 12/23/2022]
Abstract
Both reactive oxygen species (ROS) from redox-biology and pro-inflammatory cytokines from innate immunity/and other sources, in addition to their role in redox-biology, and in defense and repair, have long been regarded as potentially harmful factors associated with oxidative stress and inflammatory states. However, their important physiological functions as signaling molecules have been demonstrated to be of importance, also in Geroscience, particularly when ROS are at balanced basal levels (redox-biology) and pro-inflammatory cytokines are at very low levels (cold-inflammaging). Under these conditions, both of these components (alone or in combination) may act as signaling/response molecules involved in regulating/maintaining or restoring adaptive homeostasis during aging, particularly in the early phases of even very-mild non-damaging internal or external environmental stimuli that could nevertheless elicit low-grade warnings-signals for homeostatic stability. If signals potentially perturbing homeostasis persist, the levels of ROS and pro-inflammatory mediators increase resulting in a switch from adaptive to maladaptive responses which may lead to oxidative stress and overt-inflammaging (or even to an overt inflammatory state), thus paving the way to the risks of aging-related diseases (ARDs). Conversely, upon adaptive-responses, low-levels of ROS and very-low-levels of pro-inflammatory-cytokines, alone or in combination, can result in an amplified capacity to prevent or slow-down overt-inflammaging (2-fold to 4-fold increase of pro-inflammatory cytokines) thus maintaining or restoring homeostasis. Therefore, these signaling molecules may also have the sequential incremental potential to prevent or slow the subsequent decline of adaptive homeostasis that will occur later in the lifespan. These scenarios may lead us to conceive of, and conceptualize, both these molecules and their basal-low levels, as well as their dynamics and the time-course of responses, as 'potential important pillars of adaptive-homeostasis in aging' since the earliest phases of the occurrence of any even very- mild environmental potential imbalance.
Collapse
Affiliation(s)
- Yaqin Wei
- Department of Geriatrics, Shanghai Institute of Geriatrics, Huadong Hospital, Fudan University, Shanghai, China.
| | - Shuang Jia
- Department of Prosthodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai, China.
| | - Yuanyuan Ding
- Shanghai Medical Information Center, Shanghai Health Development Research Center, Shanghai, China.
| | - Shijin Xia
- Department of Geriatrics, Shanghai Institute of Geriatrics, Huadong Hospital, Fudan University, Shanghai, China.
| | - Sergio Giunta
- Casa di Cura Prof. Nobili-GHC Garofalo Health Care, Bologna, Italy.
| |
Collapse
|
|
3
|
Testing the Feasibility and Dietary Impact of Macaroni Fortified with Green Tea and Turmeric Curcumin Extract in Diabetic Rats. Foods 2023; 12:foods12030534. [PMID: 36766064 PMCID: PMC9914615 DOI: 10.3390/foods12030534] [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: 12/03/2022] [Revised: 01/14/2023] [Accepted: 01/16/2023] [Indexed: 01/27/2023] Open
Abstract
Macaroni is a commercially available Italian food product that is popular among consumers around the world. The supplementation of green tea extract (GTE) and turmeric curcumin extract (TCE) in macaroni may serve as promising and beneficial bioactive ingredients. We aimed to produce functional macaroni, assess the degree of consumer satisfaction and study the antidiabetic activity in diabetic rats. In this study, macaroni was fortified with GTE, TCE and a mixture of GTE and TCE ratio of 1:1, w/w (GTE/TCE). The resulting products were then analyzed in terms of their chemical compositions, while the degree of consumer satisfaction was monitored and the hypoglycemic and hypolipidemic effects in streptozotocin (STZ)-rats were investigated. GTE/TCE-M exhibited the strongest antioxidant activity (p < 0.05), while phenolics were most abundant in GTE-M. The overall preference for GTE-M, TCE-M and GTE/TCE-M were within ranges of 4.7-5.1, 5.9-6.7 and 6.2-8.2, respectively, in the nine-point hedonic scale. Consumption of these three preparations of macaroni (30 and 300 mg/kg each) neither decreased nor exacerbated increasing blood glucose levels in diabetic rats, while GTE-M (30 mg/kg) tended to lower increased serum triglyceride and cholesterol levels. In conclusion, GTE/TCE-M containing high amounts of bioactive EGCG and curcumin exerted the strongest degree of antioxidant activity and received the highest level of acceptance. Importantly, consumption of GTE-M tentatively ameliorated serum lipid abnormalities in diabetic STZ-induced rats by inhibiting lipase digestion and lipid absorption. Herein, we are proposing that GTE-fortified macaroni is a functional food that can mitigate certain metabolic syndromes.
Collapse
|
|
4
|
Himaki T, Hano K. Effects of alpha lipoic acid treatment during in vitro maturation on the development of porcine somatic cell nuclear transfer embryos. Anim Sci J 2023; 94:e13889. [PMID: 38031165 DOI: 10.1111/asj.13889] [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: 05/13/2023] [Revised: 10/08/2023] [Accepted: 10/26/2023] [Indexed: 12/01/2023]
Abstract
Oxidative stress influences the embryo production efficiency in vitro. We investigated the effects of alpha lipoic acid (ALA) treatment during the in vitro maturation (IVM) period on the porcine somatic cell nuclear transfer (SCNT) embryo production. After IVM, maturation rates of the 12.5- and 25-μM ALA-treated groups were not significantly different from those of the 0-μM ALA-treated group. Compared to those in the 0-μM ALA-treated group, the reactive oxygen species and glutathione levels were significantly decreased and increased, respectively, in the cytoplasm of matured oocytes in the 12.5-50-μM ALA-treated groups. Apoptosis rate in cumulus cells after IVM was significantly lower in the 12.5-50-μM ALA-treated groups than in the 0-μM ALA-treated group. Blastocyst formation rate was significantly higher in parthenogenetic oocytes treated with 12.5-μM ALA than in the 0-, 25-, and 50-μM ALA-treated groups. Similarly, in SCNT embryos, the 12.5-μM ALA-treated group showed a significantly higher blastocyst formation rate than the 0-μM ALA-treated group. Apoptosis rate in SCNT blastocysts was significantly decreased by 12.5-μM ALA treatment. The results showed that treatment with 12.5-μM ALA during IVM improves porcine SCNT embryo development and partial quality.
Collapse
Affiliation(s)
- Takehiro Himaki
- Department of Agricultural and Environmental Science, Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan
| | - Kazuki Hano
- Department of Agricultural and Environmental Science, Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan
| |
Collapse
|
|
5
|
Şen U, Şirin E, Önder H, Özyürek S, Kolenda M, Sitkowska B. Macromolecules Influence Cellular Competence and Expression Level of IGFs Genes in Bovine Oocytes In Vitro. Animals (Basel) 2022; 12:ani12192604. [PMID: 36230343 PMCID: PMC9558951 DOI: 10.3390/ani12192604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Revised: 09/20/2022] [Accepted: 09/27/2022] [Indexed: 11/28/2022] Open
Abstract
In vitro maturation (IVM) of mammalian oocytes, which influences subsequent in vitro development of embryos, is affected by the macromolecule content in culture media for the success of oocyte maturation competence, in which the cytoplasmic and nuclear reprogramming events occur. The insulin-like growth factor family (IGFs) promotes the maturation of bovine oocytes and the expansion of cumulus cells and also inhibits apoptosis. This study was, therefore, designed to examine the effects of macromolecules (bovine serum albumin, BSA; fetal calf serum, FCS; and polyvinyl alcohol, PVA) on in vitro nuclear maturation, total cellular protein, glutathione peroxidase (GPx) enzyme activity, and the gene expression level of IGF1, IGF2, and their receptor in bovine oocytes. Oocytes obtained from bovine ovaries were cultured in bicarbonate-buffered medium 199 supplemented with 4 mg/mL BSA, 10% FCS, 1 mg/mL PVA, and without macromolecule supplement (control) during 22 h in the air with a humidified atmosphere and 5% CO2 at 38.5 °C temperature. Supplementation of BSA and FCS increased (χ2 = 9.84; p < 0.05) the percentages of oocytes that reached metaphase II compared to the control and PVA. The amount of protein per ml of cell extracts of oocytes matured in FCS supplemented culture media was higher (p < 0.05) than the oocytes in the PVA and control. The levels of GPx enzyme activity in cell extracts isolated from oocytes in each experimental group did not change over time, but the GPx enzyme activity in oocytes matured in PVA-supplemented culture media was lower (p < 0.05) than in oocytes in the other experimental groups. Transcript for the IGF1 gene was not detected in all experimental groups, but the supplementation of BSA and FCS significantly elevated the transcript level of the IGF2 gene. In addition, the maturation of oocytes with BSA-supplemented media increased the transcript level of the IGF1R gene, whereas the transcript level of the IGF2R gene was similar among macromolecule supplementation groups. The current study concluded that BSA and FCS could improve in vitro bovine oocyte development due to supporting nuclear maturation and increasing the total cellular protein content, GPx enzyme, and transcript activity.
Collapse
Affiliation(s)
- Uğur Şen
- Department of Agricultural Biotechnology, Ondokuz Mayis University, Samsun 55139, Turkey
- Correspondence: ; Tel.: +90-3623121919/1361
| | - Emre Şirin
- Department of Agricultural Biotechnology, Kırşehir Ahi Evran University, Kırşehir 40100, Turkey
| | - Hasan Önder
- Department of Animal Science, Ondokuz Mayis University, Samsun 55139, Turkey
| | - Selçuk Özyürek
- Department of Veterinary, Erzincan Binali Yıldırım University, Erzincan 24500, Turkey
| | - Magdalena Kolenda
- Department of Animal Biotechnology and Genetic, Faculty of Animal Breeding and Biology, Bydgoszcz University of Science and Technology, 85-796 Bydgoszcz, Poland
| | - Beata Sitkowska
- Department of Animal Biotechnology and Genetic, Faculty of Animal Breeding and Biology, Bydgoszcz University of Science and Technology, 85-796 Bydgoszcz, Poland
| |
Collapse
|
|
6
|
Reversal of genetic brain iron accumulation by N,N'-bis(2-mercaptoethyl)isophthalamide, a lipophilic metal chelator, in mice. Arch Toxicol 2022; 96:1951-1962. [PMID: 35445828 DOI: 10.1007/s00204-022-03287-1] [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: 01/04/2022] [Accepted: 03/21/2022] [Indexed: 12/31/2022]
Abstract
N,N'-bis(2-mercaptoethyl)isophthalamide (NBMI) is a novel lipophilic metal chelator and antioxidant used in mercury poisoning. Recent studies have suggested that NBMI may also bind to other metals such as lead and iron. Since NBMI can enter the brain, we evaluated if NBMI removes excess iron from the iron-loaded brain and ameliorates iron-induced oxidative stress. First, NBMI exhibited preferential binding to ferrous (Fe2+) iron with a negligible binding affinity to ferric (Fe3+) iron, indicating a selective chelation of labile iron. Second, NBMI protected SH-SY5Y human neuroblastoma cells from the cytotoxic effects of high iron. NBMI also decreased cellular labile iron and lessened the production of iron-induced reactive oxygen species in these cells. Deferiprone (DFP), a commonly used oral iron chelator, failed to prevent iron-induced cytotoxicity or labile iron accumulation. Next, we validated the efficacy of NBMI in Hfe H67D mutant mice, a mouse model of brain iron accumulation (BIA). Oral gavage of NBMI for 6 weeks decreased iron accumulation in the brain as well as liver, whereas DFP showed iron chelation only in the liver, but not in the brain. Notably, depletion of brain copper and anemia were observed in BIA mice treated with DFP, but not with NBMI, suggesting a superior safety profile of NBMI over DFP for long-term use. Collectively, our study demonstrates that NBMI provides a neuroprotective effect against BIA and has therapeutic potential for neurodegenerative diseases associated with BIA.
Collapse
|
|
7
|
Mendes S, Sá R, Magalhães M, Marques F, Sousa M, Silva E. The Role of ROS as a Double-Edged Sword in (In)Fertility: The Impact of Cancer Treatment. Cancers (Basel) 2022; 14:cancers14061585. [PMID: 35326736 PMCID: PMC8946252 DOI: 10.3390/cancers14061585] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 03/17/2022] [Accepted: 03/18/2022] [Indexed: 12/22/2022] Open
Abstract
Simple Summary Tumor cells are highly resistant to oxidative stress, but beyond a certain threshold, it may lead to apoptosis/necrosis. Thus, induced loss of redox balance can be a strategy used in anticancer therapies. However, the effectiveness of drugs contrasts with unknown mechanisms involved in the loss of fertility. Considering that cancer patients’ life expectancy is increasing, it raises concerns about the unknown adverse effects. Therefore, new strategies should be pursued alongside explaining to the patients their options regarding the reproduction side effects. Abstract Tumor cells are highly resistant to oxidative stress resulting from the imbalance between high reactive oxygen species (ROS) production and insufficient antioxidant defenses. However, when intracellular levels of ROS rise beyond a certain threshold, largely above cancer cells’ capacity to reduce it, they may ultimately lead to apoptosis or necrosis. This is, in fact, one of the molecular mechanisms of anticancer drugs, as most chemotherapeutic treatments alter redox homeostasis by further elevation of intracellular ROS levels or inhibition of antioxidant pathways. In traditional chemotherapy, it is widely accepted that most therapeutic effects are due to ROS-mediated cell damage, but in targeted therapies, ROS-mediated effects are mostly unknown and data are still emerging. The increasing effectiveness of anticancer treatments has raised new challenges, especially in the field of reproduction. With cancer patients’ life expectancy increasing, many aiming to become parents will be confronted with the adverse effects of treatments. Consequently, concerns about the impact of anticancer therapies on reproductive capacity are of particular interest. In this review, we begin with a short introduction on anticancer therapies, then address ROS physiological/pathophysiological roles in both male and female reproductive systems, and finish with ROS-mediated adverse effects of anticancer treatments in reproduction.
Collapse
Affiliation(s)
- Sara Mendes
- Department of Physical Education and Sports, University Institute of Maia (ISMAI), 4475-690 Maia, Portugal;
- Research Center in Sports Sciences, Health Sciences and Human Development (CIDESD), 5001-801 Vila Real, Portugal
| | - Rosália Sá
- Laboratory of Cell Biology, Department of Microscopy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; (R.S.); (M.S.)
- Unit for Multidisciplinary Research in Biomedicine (UMIB), Laboratory for Integrative and Translational Research in Population Health (ITR), University of Porto, 4099-002 Porto, Portugal;
| | - Manuel Magalhães
- Unit for Multidisciplinary Research in Biomedicine (UMIB), Laboratory for Integrative and Translational Research in Population Health (ITR), University of Porto, 4099-002 Porto, Portugal;
- Department of Oncology, University Hospital Center of Porto (CHUP), Largo do Prof. Abel Salazar, 4099-001 Porto, Portugal;
| | - Franklim Marques
- Department of Oncology, University Hospital Center of Porto (CHUP), Largo do Prof. Abel Salazar, 4099-001 Porto, Portugal;
| | - Mário Sousa
- Laboratory of Cell Biology, Department of Microscopy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; (R.S.); (M.S.)
- Unit for Multidisciplinary Research in Biomedicine (UMIB), Laboratory for Integrative and Translational Research in Population Health (ITR), University of Porto, 4099-002 Porto, Portugal;
| | - Elisabete Silva
- Laboratory of General Physiology, Department of Immuno-Physiology and Pharmacology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
- Institute for Molecular and Cell Biology (IBMC), Institute for Research & Innovation in Health (I3S), University of Porto, Rua Alfredo Allen, 4200-135 Porto, Portugal
- Correspondence:
| |
Collapse
|
|
8
|
Mechanistic Insights of Chelator Complexes with Essential Transition Metals: Antioxidant/Pro-Oxidant Activity and Applications in Medicine. Int J Mol Sci 2022; 23:ijms23031247. [PMID: 35163169 PMCID: PMC8835618 DOI: 10.3390/ijms23031247] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 01/13/2022] [Accepted: 01/20/2022] [Indexed: 12/24/2022] Open
Abstract
The antioxidant/pro-oxidant activity of drugs and dietary molecules and their role in the maintenance of redox homeostasis, as well as the implications in health and different diseases, have not yet been fully evaluated. In particular, the redox activity and other interactions of drugs with essential redox metal ions, such as iron and copper, need further investigation. These metal ions are ubiquitous in human nutrition but also widely found in dietary supplements and appear to exert major effects on redox homeostasis in health, but also on many diseases of free radical pathology. In this context, the redox mechanistic insights of mainly three prototype groups of drugs, namely alpha-ketohydroxypyridines (alpha-hydroxypyridones), e.g., deferiprone, anthraquinones, e.g., doxorubicin and thiosemicarbazones, e.g., triapine and their metal complexes were examined; details of the mechanisms of their redox activity were reviewed, with emphasis on the biological implications and potential clinical applications, including anticancer activity. Furthermore, the redox properties of these three classes of chelators were compared to those of the iron chelating drugs and also to vitamin C, with an emphasis on their potential clinical interactions and future clinical application prospects in cancer, neurodegenerative and other diseases.
Collapse
|
|
9
|
Zaki SM, Waggas DS. Protective Effect of Nigella sativa and Onion Extract against 5-Fluorouracil-Induced Hepatic Toxicity. Nutr Cancer 2021; 74:2657-2670. [PMID: 34963383 DOI: 10.1080/01635581.2021.2019794] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Aim: The present study intended to compare the antioxidant, anti-lipid peroxidation, and anti-inflammatory potentials of Nigella Sativa (NS) and onion extract on 5-FU-induced liver damage in rats. Material and methods: 48 rats were divided into control, control group of the onion extract, control group of the NS extract, 5-FU-treated, concomitant NS-treated, and concomitant onion extract-treated. Liver sections were processed for histological analysis (light and electron microscopic examination). Liver enzymes (ALT, AST, and ALP), inflammatory markers (TNF-α and IL-1), antioxidant markers (SOD, GSH, and GSH/GSSG ratio), 4-HNE, NF-κB, and Nrf2 were evaluated. Results: The 5-FU-treated group exhibited inflammation, congested hepatic sinusoid, and steatosis. Improvement with few pathological residues was seen in the concomitant extract-treated groups. The 5-FU-treated group showed higher liver enzymes. The enzymes decreased in the concomitantly treated groups. 5-FU induced liver damage through oxidative stress, inflammation, and lipid peroxidation. Concomitantly using NS and onion extracts resulted in a reduction in oxidative stress, lipid peroxidation, and inflammation. Conclusion: NS and onion extracts attenuated 5-FU-induced liver damage via antioxidative, anti-lipid peroxidative, and anti-inflammatory mechanisms. NS's role was exceptional when compared with onion extract.
Collapse
Affiliation(s)
- Sherif Mohamed Zaki
- Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia.,Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Dania S Waggas
- Department of pharmacology, Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia
| |
Collapse
|
|
10
|
Khurana K, Kumar M, Bansal N. Lacidipine Attenuates Symptoms of Nicotine Withdrawal in Mice. Neurotox Res 2021; 39:1920-1936. [PMID: 34613588 DOI: 10.1007/s12640-021-00421-2] [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: 07/11/2021] [Revised: 07/11/2021] [Accepted: 09/17/2021] [Indexed: 11/24/2022]
Abstract
Nicotine-withdrawal after daily exposure manifests somatic and affective symptom including a range of cognitive deficits. Earlier studies suggested participation of L-type calcium channels (LTCCs) in development of nicotine dependence and expression of withdrawal signs. An upsurge in Ca2+-induced oxidative stress in brain underlies the biochemical events and behavioral signs of nicotine-withdrawal. The present study is aimed to explore the effects of lacidipine (LTCC antagonist) against nicotine-withdrawal. Swiss albino mice were administered ( -)-nicotine hydrogen tartrate (3.35 mg/kg, t.i.d.) from days 1 to 7 and alongside lacidipine (0.3, 1, and 3 mg/kg, i.p.) given from days 1 to 14. Somatic withdrawal signs were noted 48 h after last dose of nicotine. Bay-K8644 (LTCC agonist) was administered in mice subjected to nicotine-withdrawal and lacidipine (3 mg/kg) treatments. Behavioral tests of memory, anxiety, and depression were conducted on days 13 and 14 to assess the effects of lacidipine on affective symptoms of nicotine-withdrawal. Biomarkers of oxido-nitrosative were quantified in the whole brain. Nicotine-withdrawal significantly enhanced somatic signs and symptoms of anxiety, depression, and memory impairment in mice. Lacidipine (1 and 3 mg/kg) attenuated nicotine-withdrawal induced somatic symptoms and also ameliorated behavioral abnormalities. Nicotine-withdrawal triggered an upsurge in brain lipid peroxidation, total nitrite content, and decline in antioxidants, and these effects were attenuated by lacidipine. Bay-K8644 significantly abolished improvement in somatic and affective symptoms, and antioxidant effects by lacidipine in mice subjected to nicotine-withdrawal. Lacidipine mitigated nicotine-withdrawal triggered somatic and affective symptoms owing to decrease in brain oxido-nitrosative stress.
Collapse
Affiliation(s)
- Kunal Khurana
- I. K. Gujral Punjab Technical University, Kapurthala (Punjab) 144603, India
- Department of Pharmacology, Amar Shaheed Baba Ajit Singh Jujhar Singh Memorial College of Pharmacy, Bela (Ropar) 140111, India
| | - Manish Kumar
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Nitin Bansal
- Department of Pharmacology, Amar Shaheed Baba Ajit Singh Jujhar Singh Memorial College of Pharmacy, Bela (Ropar) 140111, India.
- Department of Pharmaceutical Sciences, Chaudhary Bansi Lal University (CBLU), Bhiwani, Haryana, 127021, India.
| |
Collapse
|
|
11
|
Abstract
The aim of this study was to evaluate follicular development, morphological integrity, and antioxidant potential of preantral ovarian follicles from Bos taurus indicus females grown in vitro with alpha-lipoic acid. Ovaries (n = 24) of Bos taurus indicus (n = 12) females were collected during slaughter and fragmented. A randomly obtained fragment from each pair of ovaries was fixed in Bouin (non-cultivated control; D0). These fragments were intended for classical histology (morphology and evaluation of follicular growth), and a fragment from each pair of ovaries was frozen at -80°C (non-cultivated control; D0), and assigned for analysis of oxidative stress [thiobarbituric acid reactive substances (TBARS), nitroblue tetrazolium (NBT), and ferric reducing antioxidant power (FRAP)]. The remaining fragments were cultured in vitro for 6 (D6) or 12 (D12) days, containing only minimum essential medium (MEM) or MEM supplemented with alpha-lipoic acid (50, 100, or 250 ng/ml), on an extracellular matrix of agarose gel, in an oven at 38.5ºC. Every 2 days, 100% of the culture medium was replaced. Supplementation with 100 ng/ml was effective for maintaining follicular integrity after 6 days of culture (primordial: 51.28%; development: 36.88%; P < 0.0001). There was no difference (P > 0.05) between treatments compared with the non-cultivated control treatment (D0), using the NBT and TBARS assays. Therefore, supplementation of the in vitro culture medium of bovine preantral ovarian follicles with a concentration of 100 ng/ml of alpha-lipoic acid at 6 days of culture was effective for maintaining follicular integrity and, after 6 days, maintaining stable levels of reactive oxygen species.
Collapse
|
|
12
|
Patnaik P, Sahoo DD. Variations in oxidative stress and antioxidant defense level during different phases of hibernation in common Asian toad, Duttaphrynus melanostictus. Biol Open 2021; 10:bio058567. [PMID: 34350459 PMCID: PMC8353263 DOI: 10.1242/bio.058567] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Accepted: 06/07/2021] [Indexed: 12/12/2022] Open
Abstract
To assess redox status during hibernation with metabolic depression, oxidative stress parameters and antioxidant defense were assessed during different phases of hibernation including active period, hibernation, arousal, and post-arousal period, in the liver and brain tissues of Duttaphrynus melanostictus. We hypothesized low levels of oxidative stress and antioxidant defense during the hibernation period in comparison to the summer active period, due to hypometabolism and their subsequent increase during the arousal period following an increase in body temperature and metabolism. Contrary to our hypothesis, increased oxidative stress with significantly higher lipid peroxidation, protein carbonylation, oxidized glutathione (GSSG): glutathione (GSH) ratio, and elevated antioxidants defense consisting of higher catalase activity and high ascorbic acid content to control oxidative stress were found during hibernation. However, GSH and uric acid levels were found low with super oxide dismutase (SOD) activities at a steady level during hibernation. Supporting our hypothesis, increased oxidative stress with high lipid peroxidation and GSSG:GSH ratio were found during arousal from hibernation owing to increased oxygen consumption and rewarming. Augmented catalase and SOD activities and nonenzymatic antioxidants (GSH, ascorbic acid, and uric acid) level were found to counteract oxidative stress during arousal periods as it was expected. A steady level of protein carbonylation, indicating no oxidative damage during arousal from hibernation due to elevated antioxidant defense, shows the significance of hibernation to overcome food and water scarcity and cold climatic condition. Decrease in antioxidants levels accompanying coming down of lipid peroxidation, protein carbonylation, and GSSG:GSH ratio to their lower levels during the post-arousal period showing normalcy in redox status as it was during active period indicates controllability of oxidative stress in hibernating toads.
Collapse
Affiliation(s)
- Prabhati Patnaik
- Assistant Scientific Officer, Regional Forensic Science Laboratory, Berhampur, Odisha 760007, India
| | - Deba Das Sahoo
- Post-Graduate Department of Zoology, S.C.S Autonomous College, Puri, Odisha 752001, India
| |
Collapse
|
|
13
|
Sullivan KE, Mylniczenko ND, Nelson SE, Coffin B, Lavin SR. Practical Management of Iron Overload Disorder (IOD) in Black Rhinoceros (BR; Diceros bicornis). Animals (Basel) 2020; 10:ani10111991. [PMID: 33138144 PMCID: PMC7692874 DOI: 10.3390/ani10111991] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 10/23/2020] [Accepted: 10/26/2020] [Indexed: 12/13/2022] Open
Abstract
Simple Summary Black rhinoceros under human care are predisposed to Iron Overload Disorder that is unlike the hereditary condition seen in humans. We aim to address the black rhino caretaker community at multiple perspectives (keeper, curator, veterinarian, nutritionist, veterinary technician, and researcher) to describe approaches to Iron Overload Disorder in black rhinos and share learnings. This report includes sections on (1) background on how iron functions in comparative species and how Iron Overload Disorder appears to work in black rhinos, (2) practical recommendations for known diagnostics, (3) a brief review of current investigations on inflammatory and other potential biomarkers, (4) nutrition knowledge and advice as prevention, and (5) an overview of treatment options including information on chelation and details on performing large volume voluntary phlebotomy. The aim is to use evidence to support the successful management of this disorder to ensure optimal animal health, welfare, and longevity for a sustainable black rhinoceros population. Abstract Critically endangered black rhinoceros (BR) under human care are predisposed to non-hemochromatosis Iron Overload Disorder (IOD). Over the last 30 years, BR have been documented with diseases that have either been induced by or exacerbated by IOD, prompting significant efforts to investigate and address this disorder. IOD is a multi-factorial chronic disease process requiring an evidence-based and integrative long-term approach. While research continues to elucidate the complexities of iron absorption, metabolism, and dysregulation in this species, preventive treatments are recommended and explained herein. The aim of this report is to highlight the accumulated evidence in nutrition, clinical medicine, and behavioral husbandry supporting the successful management of this disorder to ensure optimal animal health, welfare, and longevity for a sustainable black rhinoceros population.
Collapse
|
|
14
|
Modulation and Protection Effects of Antioxidant Compounds against Oxidant Induced Developmental Toxicity in Zebrafish. Antioxidants (Basel) 2020; 9:antiox9080721. [PMID: 32784515 PMCID: PMC7463582 DOI: 10.3390/antiox9080721] [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] [Received: 07/22/2020] [Accepted: 08/04/2020] [Indexed: 12/15/2022] Open
Abstract
The antioxidant effect of compounds is regularly evaluated by in vitro assays that do not have the capability to predict in vivo protective activity or to determine their underlying mechanisms of action. The aim of this study was to develop an experimental system to evaluate the in vivo protective effects of different antioxidant compounds, based on the zebrafish embryo test. Zebrafish embryos were exposed to tert-butyl hydroperoxide (tBOOH), tetrachlorohydroquinone (TCHQ) and lipopolysaccharides from Escherichia coli (LPS), chemicals that are known inducers of oxidative stress in zebrafish. The developmental toxic effects (lethality or dysmorphogenesis) induced by these chemicals were modulated with n-acetyl l-cysteine and Nω-nitro l-arginine methyl ester hydrochloride, dimethyl maleate and dl-buthionine sulfoximine in order to validate the oxidant mechanism of oxidative stress inducers. The oxidant effects of tBOOH, TCHQ, and LPS were confirmed by the determination of significant differences in the comparison between the concentration–response curves of the oxidative stress inducers and of the modulators of antioxidant status. This concept was also applied to the study of the effects of well-known antioxidants, such as vitamin E, quercetin, and lipoic acid. Our results confirm the zebrafish model as an in vivo useful tool to test the protective effects of antioxidant compounds.
Collapse
|
|
15
|
Trying to Solve the Puzzle of the Interaction of Ascorbic Acid and Iron: Redox, Chelation and Therapeutic Implications. MEDICINES 2020; 7:medicines7080045. [PMID: 32751493 PMCID: PMC7460366 DOI: 10.3390/medicines7080045] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 07/28/2020] [Accepted: 07/28/2020] [Indexed: 02/06/2023]
Abstract
Iron and ascorbic acid (vitamin C) are essential nutrients for the normal growth and development of humans, and their deficiency can result in serious diseases. Their interaction is of nutritional, physiological, pharmacological and toxicological interest, with major implications in health and disease. Millions of people are using pharmaceutical and nutraceutical preparations of these two nutrients, including ferrous ascorbate for the treatment of iron deficiency anaemia and ascorbate combination with deferoxamine for increasing iron excretion in iron overload. The main function and use of vitamin C is its antioxidant activity against reactive oxygen species, which are implicated in many diseases of free radical pathology, including biomolecular-, cellular- and tissue damage-related diseases, as well as cancer and ageing. Ascorbic acid and its metabolites, including the ascorbate anion and oxalate, have metal binding capacity and bind iron, copper and other metals. The biological roles of ascorbate as a vitamin are affected by metal complexation, in particular following binding with iron and copper. Ascorbate forms a complex with Fe3+ followed by reduction to Fe2+, which may potentiate free radical production. The biological and clinical activities of iron, ascorbate and the ascorbate–iron complex can also be affected by many nutrients and pharmaceutical preparations. Optimal therapeutic strategies of improved efficacy and lower toxicity could be designed for the use of ascorbate, iron and the iron–ascorbate complex in different clinical conditions based on their absorption, distribution, metabolism, excretion, toxicity (ADMET), pharmacokinetic, redox and other properties. Similar strategies could also be designed in relation to their interactions with food components and pharmaceuticals, as well as in relation to other aspects concerning personalized medicine.
Collapse
|
|
16
|
Terao H, Wada‐Hiraike O, Nagumo A, Kunitomi C, Azhary JMK, Harada M, Hirata T, Hirota Y, Koga K, Fujii T, Osuga Y. Role of oxidative stress in follicular fluid on embryos of patients undergoing assisted reproductive technology treatment. J Obstet Gynaecol Res 2019; 45:1884-1891. [DOI: 10.1111/jog.14040] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Accepted: 05/29/2019] [Indexed: 01/16/2023]
Affiliation(s)
- Hiromi Terao
- Department of Obstetrics and Gynecology, Graduate School of MedicineThe University of Tokyo Tokyo Japan
| | - Osamu Wada‐Hiraike
- Department of Obstetrics and Gynecology, Graduate School of MedicineThe University of Tokyo Tokyo Japan
| | - Aiko Nagumo
- Department of Obstetrics and Gynecology, Graduate School of MedicineThe University of Tokyo Tokyo Japan
| | - Chisato Kunitomi
- Department of Obstetrics and Gynecology, Graduate School of MedicineThe University of Tokyo Tokyo Japan
| | - Jerilee M. K. Azhary
- Department of Obstetrics and Gynecology, Graduate School of MedicineThe University of Tokyo Tokyo Japan
| | - Miyuki Harada
- Department of Obstetrics and Gynecology, Graduate School of MedicineThe University of Tokyo Tokyo Japan
| | - Tetsuya Hirata
- Department of Obstetrics and Gynecology, Graduate School of MedicineThe University of Tokyo Tokyo Japan
| | - Yasushi Hirota
- Department of Obstetrics and Gynecology, Graduate School of MedicineThe University of Tokyo Tokyo Japan
| | - Kaori Koga
- Department of Obstetrics and Gynecology, Graduate School of MedicineThe University of Tokyo Tokyo Japan
| | - Tomoyuki Fujii
- Department of Obstetrics and Gynecology, Graduate School of MedicineThe University of Tokyo Tokyo Japan
| | - Yutaka Osuga
- Department of Obstetrics and Gynecology, Graduate School of MedicineThe University of Tokyo Tokyo Japan
| |
Collapse
|
|
17
|
Saharkhiz bandforouzi K, Rezaei M, KazemiFard M. Effects of Different Levels of Tomato Powder with and without Addition of Enzymes on Performance, Blood Parameters and Antioxidant Status of Japanese Quails. ACTA ACUST UNITED AC 2019. [DOI: 10.29252/rap.10.23.11] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
|
|
18
|
Anasooya Shaji C, Robinson BD, Yeager A, Beeram MR, Davis ML, Isbell CL, Huang JH, Tharakan B. The Tri-phasic Role of Hydrogen Peroxide in Blood-Brain Barrier Endothelial cells. Sci Rep 2019; 9:133. [PMID: 30644421 PMCID: PMC6333800 DOI: 10.1038/s41598-018-36769-3] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Accepted: 11/21/2018] [Indexed: 12/11/2022] Open
Abstract
Hydrogen peroxide (H2O2) plays an important role physiologically as the second messenger and pathologically as an inducer of oxidative stress in injury, ischemia and other conditions. However, it is unclear how H2O2 influences various cellular functions in health and disease differentially, particularly in the blood-brain barrier (BBB). We hypothesized that the change in cellular concentrations of H2O2 is a major contributor in regulation of angiogenesis, barrier integrity/permeability and cell death/apoptosis in BBB endothelial cells. Rat brain microvascular endothelial cells were exposed to various concentrations of H2O2 (1 nM to 25 mM). BBB tight junction protein (zonula ocludens-1; ZO-1) localization and expression, cytoskeletal organization, monolayer permeability, angiogenesis, cell viability and apoptosis were evaluated. H2O2 at low concentrations (0.001 μM to 1 μM) increased endothelial cell tube formation indicating enhanced angiogenesis. H2O2 at 100 μM and above induced monolayer hyperpermeability significantly (p < 0.05). H2O2 at 10 mM and above decreased cell viability and induced apoptosis (p < 0.05). There was a decrease of ZO-1 tight junction localization with 100 μm H2O2, but had no effect on protein expression. Cytoskeletal disorganizations were observed starting at 1 μm. In conclusion H2O2 influences angiogenesis, permeability, and cell death/apoptosis in a tri-phasic and concentration-dependent manner in microvascular endothelial cells of the blood-brain barrier.
Collapse
Affiliation(s)
- Chinchusha Anasooya Shaji
- Department of Surgery, Texas A&M University Health Science Center College of Medicine and Baylor Scott & White Health, Temple, Texas, USA
| | - Bobby D Robinson
- Department of Surgery, Texas A&M University Health Science Center College of Medicine and Baylor Scott & White Health, Temple, Texas, USA
| | - Antonia Yeager
- Department of Surgery, Texas A&M University Health Science Center College of Medicine and Baylor Scott & White Health, Temple, Texas, USA
| | - Madhava R Beeram
- Department of Pediatrics, Texas A&M University Health Science Center College of Medicine and Baylor Scott & White Health, Temple, Texas, USA
| | - Matthew L Davis
- Department of Surgery, Texas A&M University Health Science Center College of Medicine and Baylor Scott & White Health, Temple, Texas, USA
| | - Claire L Isbell
- Department of Surgery, Texas A&M University Health Science Center College of Medicine and Baylor Scott & White Health, Temple, Texas, USA
| | - Jason H Huang
- Department of Neurosurgery, Texas A&M University Health Science Center College of Medicine and Baylor Scott & White Health, Temple, Texas, USA
| | - Binu Tharakan
- Department of Surgery, Texas A&M University Health Science Center College of Medicine and Baylor Scott & White Health, Temple, Texas, USA.
| |
Collapse
|
|
19
|
Aydogan Mathyk B, Aslan Cetin B, Vardagli D, Zengin E, Sofiyeva N, Irez T, Ocal P. Comparison of antagonist mild and long agonist protocols in terms of follicular fluid total antioxidant capacity. Taiwan J Obstet Gynecol 2018; 57:194-199. [PMID: 29673660 DOI: 10.1016/j.tjog.2018.02.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/18/2017] [Indexed: 10/17/2022] Open
Abstract
OBJECTIVE A high dose of prolonged gonadotropins can yield higher numbers of oocytes and embryos. The high dose or prolonged regimens can be associated with ovarian hyperstimulation syndrome (OHSS), multiple gestations, emotional stress, economical burden and treatment dropout. In mild stimulation lower doses and shorter duration times of gonadotropin are used in contrast to the conventional long stimulation protocol in IVF. It has been proposed that supraphysiologic levels of hormones may adversely affect endometrium and oocyte/embryo. Also it has been proposed that oxidative stress (OS) may alter ovarian hormone dynamics and could be further affected by additional exogenous hormonal stimulation. Therefore our aim was to compare follicular fluid total antioxidant capacity (TAC) in antagonist mild and long agonist stimulations. MATERIALS AND METHODS Forty patients received antagonist mild stimulation, starting on the 5th day of their cycle and forty patients received long agonist treatment. Seventy-five patients undergoing their first IVF cycle were included in the final analysis. Follicular fluid (FF) samples were analyzed for estradiol (E2), antimullerian hormone (AMH) and TAC. RESULTS FF-Total antioxidant capacity (TAC) levels were higher in the long agonist group as opposed to the antagonist group [1.07 ± 0.04 mmol Trolox equivalent/L vs 1 ± 0.13 mmol Trolox equivalent/L] (Fig. 1). Pregnancy rates were not significantly different between the two treatments. The FF-TAC levels were not different among infertility etiologies (Fig. 3). FF-TAC levels did not have a direct correlation with pregnancy but a positive correlation with the total gonadotropin dose was observed. CONCLUSION Patients with good ovarian reserves and under the age of 35 effectively responded to mild stimulation treatment. Using lower amounts of gonadotropin, yielded less FF-TAC levels in patients who underwent antagonist mild protocol. In patients under the age of 35, antagonist mild stimulation is a patient friendly and effective procedure when undergoing their first IVF cycle.
Collapse
Affiliation(s)
- Begum Aydogan Mathyk
- Istanbul University Cerrahpasa Faculty of Medicine, Department of Obstetrics and Gynecology, Istanbul, Turkey.
| | - Berna Aslan Cetin
- Kanuni Sultan Suleyman Research and Training Hospital, Department of Obstetrics and Gynecology, Istanbul, Turkey
| | - Duygu Vardagli
- Istanbul Esenyurt University Medical Laboratory Technologies, Istanbul, Turkey
| | - Emel Zengin
- Istanbul University Cerrahpasa Faculty of Medicine, Department of Biochemistry, Istanbul, Turkey
| | - Nigar Sofiyeva
- Yale University School of Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, New Haven, 06510, CT, USA
| | - Tulay Irez
- Biruni University Faculty of Medicine, Department of Histology and Embryology, Istanbul, Turkey
| | - Pelin Ocal
- Istanbul University Cerrahpasa Faculty of Medicine, Department of Obstetrics and Gynecology, Istanbul, Turkey
| |
Collapse
|
|
20
|
Liu Y, Cheng Y, Li J, Wang Y, Liu Y. Epoxy Stearic Acid, an Oxidative Product Derived from Oleic Acid, Induces Cytotoxicity, Oxidative Stress, and Apoptosis in HepG2 Cells. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2018; 66:5237-5246. [PMID: 29730927 DOI: 10.1021/acs.jafc.8b01954] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
In the present study, effects of cis-9,10-epoxy stearic acid (ESA) generated by the thermal oxidation of oleic acid on HepG2 cells, including cytotoxicity, apoptosis, and oxidative stress, were investigated. Our results revealed that ESA decreased the cell viability and induced cell death. Cell cycle analysis with propidium iodide staining showed that ESA induced cell cycle arrest at the G0/G1 phase in HepG2 cells. Cell apoptosis analysis with annexin V and propidium iodide staining demonstrated that ESA induced HepG2 cell apoptotic events in a dose- and time-dependent manner; the apoptosis of cells after treated with 500 μM ESA for 12, 24, and 48 h was 32.16, 38.70, and 65.80%, respectively. Furthermore, ESA treatment to HepG2 cells resulted in an increase in reactive oxygen species and malondialdehyde (from 0.84 ± 0.02 to 8.90 ± 0.50 nmol/mg of protein) levels and a reduction in antioxidant enzyme activity, including superoxide dismutase (from 1.34 ± 0.27 to 0.10 ± 0.007 units/mg of protein), catalase (from 100.04 ± 5.05 to 20.09 ± 3.00 units/mg of protein), and glutathione peroxidase (from 120.44 ± 7.62 to 35.84 ± 5.99 milliunits/mg of protein). These findings provide critical information on the effects of ESA on HepG2 cells, particularly cytotoxicity and oxidative stress, which is important for the evaluation of the biosafety of the oxidative product of oleic acid.
Collapse
Affiliation(s)
- Ying Liu
- School of Food Science and Technology, Synergetic Innovation Center of Food Safety and Nutrition , Jiangnan University , 1800 Lihu Avenue , Wuxi , Jiangsu 214122 , People's Republic of China
| | - Yajun Cheng
- School of Food Science and Technology, Synergetic Innovation Center of Food Safety and Nutrition , Jiangnan University , 1800 Lihu Avenue , Wuxi , Jiangsu 214122 , People's Republic of China
| | - Jinwei Li
- School of Food Science and Technology, Synergetic Innovation Center of Food Safety and Nutrition , Jiangnan University , 1800 Lihu Avenue , Wuxi , Jiangsu 214122 , People's Republic of China
| | - Yuanpeng Wang
- School of Food Science and Technology, Synergetic Innovation Center of Food Safety and Nutrition , Jiangnan University , 1800 Lihu Avenue , Wuxi , Jiangsu 214122 , People's Republic of China
| | - Yuanfa Liu
- School of Food Science and Technology, Synergetic Innovation Center of Food Safety and Nutrition , Jiangnan University , 1800 Lihu Avenue , Wuxi , Jiangsu 214122 , People's Republic of China
| |
Collapse
|
|
21
|
Orban JC, Singer M. Oxygen and Oxidative Stress. METABOLIC DISORDERS AND CRITICALLY ILL PATIENTS 2018:431-439. [DOI: 10.1007/978-3-319-64010-5_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
22
|
Alpha lipoic acid (ALA) effects on developmental competence of equine preantral follicles in short-term culture. Theriogenology 2018; 105:169-173. [DOI: 10.1016/j.theriogenology.2017.09.023] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Revised: 09/10/2017] [Accepted: 09/17/2017] [Indexed: 11/15/2022]
|
|
23
|
Berger MM, Jia XY, Legay V, Aymard M, Tilles JG, Lina B. Nutrition- and Virus-Induced Stress Represses the Expression of Manganese Superoxide Dismutase in Vitro. Exp Biol Med (Maywood) 2016; 229:843-9. [PMID: 15337840 DOI: 10.1177/153537020422900818] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
The relationship between oxidative stress and neuronal cell death has been suggested for many years. To understand the influence of oxidative stress on neuronal cell death, we investigated the influence of oxidative stress on DEV cells, a human glial cell line. Using enterovirus infection and/or malnutrition to induce oxidative stress, our results demonstrate that those stressors severely influence the antioxidant defense system in DEV cells. Although the expression of mitochondrial manganese superoxide dismutase (MnSOD) in DEV cells was significantly increased in acute infection with viral and nutritional stress, in persistent infection and nutritional stress, the expression of the MnSOD was drastically downregulated. We believe that this downregulation of MnSOD expression in the chronic stress model is due to repression of antioxidant defense. The downregulation of the MnSOD expression may lead to an increase of free-radical production and thus explain why the cells in the chronic stress model were more vulnerable to other oxidative stress influences. The vulnerability of DEV cells to additional stress factors resulted in progressive cell death, which may be analogous to the cell death in neurodegenerative diseases.
Collapse
Affiliation(s)
- Martina M Berger
- Department of Medicine, University of California, Irvine, Orange, California 92868, USA.
| | | | | | | | | | | |
Collapse
|
|
24
|
Kontoghiorghe CN, Kontoghiorghes GJ. New developments and controversies in iron metabolism and iron chelation therapy. World J Methodol 2016; 6:1-19. [PMID: 27019793 PMCID: PMC4804243 DOI: 10.5662/wjm.v6.i1.1] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2015] [Revised: 11/17/2015] [Accepted: 12/17/2015] [Indexed: 02/06/2023] Open
Abstract
Iron is essential for all organisms including microbial, cancer and human cells. More than a quarter of the human population is affected by abnormalities of iron metabolism, mainly from iron deficiency and iron overload. Iron also plays an important role in free radical pathology and oxidative damage which is observed in almost all major diseases, cancer and ageing. New developments include the complete treatment of iron overload and reduction of morbidity and mortality in thalassaemia using deferiprone and selected deferiprone/deferoxamine combinations and also the use of the maltol iron complex in the treatment of iron deficiency anaemia. There is also a prospect of using deferiprone as a universal antioxidant in non iron overloaded diseases such as neurodegenerative, cardiovascular, renal, infectious diseases and cancer. New regulatory molecules of iron metabolism such as endogenous and dietary chelating molecules, hepcidin, mitochondrial ferritin and their role in health and disease is under evaluation. Similarly, new mechanisms of iron deposition, removal, distribution and toxicity have been identified using new techniques such as magnetic resonance imaging increasing our understanding of iron metabolic processes and the targeted treatment of related diseases. The uniform distribution of iron in iron overload between organs and within each organ is no longer valid. Several other controversies such as the toxicity impact of non transferrin bound iron vs injected iron, the excess levels of iron in tissues causing toxicity and the role of chelation on iron absorption need further investigation. Commercial interests of pharmaceutical companies and connections to leading journals are playing a crucial role in shaping worldwide medical opinion on drug sales and use but also patients' therapeutic outcome and safety. Major controversies include the selection criteria and risk/benefit assessment in the use of deferasirox in thalassaemia and more so in idiopathic haemochromatosis, thalassaemia intermedia and ex-thalassaemia transplanted patients who are safely treated with venesection. Iron chelating drugs can override normal regulatory pathways, correct iron imbalance and minimise iron toxicity. The use of iron chelating drugs as main, alternative or adjuvant therapy is in progress in many conditions, especially those with non established or effective therapies.
Collapse
|
|
25
|
Kontoghiorghe CN, Kontoghiorghes GJ. Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion-dependent thalassemia syndromes. DRUG DESIGN DEVELOPMENT AND THERAPY 2016; 10:465-81. [PMID: 26893541 PMCID: PMC4745840 DOI: 10.2147/dddt.s79458] [Citation(s) in RCA: 102] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The prevalence rate of thalassemia, which is endemic in Southeast Asia, the Middle East, and the Mediterranean, exceeds 100,000 live births per year. There are many genetic variants in thalassemia with different pathological severity, ranging from a mild and asymptomatic anemia to life-threatening clinical effects, requiring lifelong treatment, such as regular transfusions in thalassemia major (TM). Some of the thalassemias are non-transfusion-dependent, including many thalassemia intermedia (TI) variants, where iron overload is caused by chronic increase in iron absorption due to ineffective erythropoiesis. Many TI patients receive occasional transfusions. The rate of iron overloading in TI is much slower in comparison to TM patients. Iron toxicity in TI is usually manifested by the age of 30-40 years, and in TM by the age of 10 years. Subcutaneous deferoxamine (DFO), oral deferiprone (L1), and DFO-L1 combinations have been effectively used for more than 20 years for the treatment of iron overload in TM and TI patients, causing a significant reduction in morbidity and mortality. Selected protocols using DFO, L1, and their combination can be designed for personalized chelation therapy in TI, which can effectively and safely remove all the excess toxic iron and prevent cardiac, liver, and other organ damage. Both L1 and DF could also prevent iron absorption. The new oral chelator deferasirox (DFX) increases iron excretion and decreases liver iron in TM and TI. There are drawbacks in the use of DFX in TI, such as limitations related to dose, toxicity, and cost, iron load of the patients, and ineffective removal of excess iron from the heart. Furthermore, DFX appears to increase iron and other toxic metal absorption. Future treatments of TI and related iron-loading conditions could involve the use of the iron-chelating drugs and other drug combinations not only for increasing iron excretion but also for preventing iron absorption.
Collapse
Affiliation(s)
| | - George J Kontoghiorghes
- Postgraduate Research Institute of Science, Technology, Environment and Medicine, Limassol, Cyprus
| |
Collapse
|
|
26
|
Hwang SU, Jeon Y, Yoon JD, Cai L, Kim E, Yoo H, Kim KJ, Park KM, Jin M, Kim H, Hyun SH. Effect of ganglioside GT1b on the in vitro maturation of porcine oocytes and embryonic development. J Reprod Dev 2015; 61:549-57. [PMID: 26370787 PMCID: PMC4685221 DOI: 10.1262/jrd.2015-049] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Ganglioside is an acidic glycosphingolipid with sialic acids residues. This study was performed to investigate the effect and mechanism of ganglioside GT1b in porcine oocytes in the process of in vitro maturation (IVM) and preimplantation development. Metaphase II (MII) rates were significantly (P < 0.05) different between the control group and the 5 nM GT1b treatment group. Intracellular glutathione (GSH) levels in oocytes matured with 5 nM and 20 nM and GT1b decreased significantly (P < 0.05). The 10 nM group showed a significant (P < 0.05) decrease in intracellular reactive oxygen species (ROS) levels compared with the control group. Subsequently, the level of intracellular Ca(2+) in oocytes treated with different concentrations of GT1b was measured. Intracellular Ca(2+) was significantly (P < 0.05) increased with a higher concentration of GT1b in a dose-dependent manner. Real-time PCR was performed and showed that the expression of bradykinin 2 receptor (B2R) and calcium/calmodulin-dependent protein kinase II delta (CaMKIIδ) in cumulus cells was significantly (P < 0.05) decreased in the 20 nM GT1b treatment group. Treatment with 5 nM GT1b significantly (P < 0.05) decreased the expression of CaMKIIδ. In oocytes, treatment with 5 nM GT1b significantly (P < 0.05) decreased CaMKIIγ and POU5F1 (POU domain, class 5, transcription factor 1). However, treatment with 20 nM GT1b significantly (P < 0.05) increased the expression of POU5F1. Finally, embryonic developmental data showed no significant differences in the two experiments (parthenogenesis and in vitro fertilization). In conclusion, the results of the present study indicated that GT1b plays an important role in increasing the nuclear maturation rate and decreasing the intracellular ROS levels during IVM. However, GT1b inhibited maturation of the cytoplasm by maintaining intracellular Ca(2+) in the process of oocyte maturation regardless of the cell cycle stage. Therefore, GT1b is thought to act on another mechanism that controls intracellular Ca(2+).
Collapse
Affiliation(s)
- Seon-Ung Hwang
- Laboratory of Veterinary Embryology and Biotechnology, College of Veterinary Medicine, Chungbuk National University, Chungbuk 362-763, South Korea
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
27
|
Rosita G, Manuel C, Franco M, Cinzia N, Donatella F, Emiliano L, Luca M, Roberta G. Permethrin and its metabolites affect Cu/Zn superoxide conformation: fluorescence and in silico evidences. MOLECULAR BIOSYSTEMS 2015; 11:208-17. [DOI: 10.1039/c4mb00491d] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Permethrin and its metabolites affect the structure and activity of Cu/Zn superoxide dismutase (SOD), as it results from intrinsic fluorescence, 8-ANS fluorescence techniques and in silico studies.
Collapse
Affiliation(s)
- Gabbianelli Rosita
- Scuola del Farmaco e dei Prodotti della Salute Università di Camerino
- Via Gentile III da Varano
- Camerino
- Italy
| | - Carloni Manuel
- Scuola del Farmaco e dei Prodotti della Salute Università di Camerino
- Via Gentile III da Varano
- Camerino
- Italy
| | - Marmocchi Franco
- Scuola del Farmaco e dei Prodotti della Salute Università di Camerino
- Via Gentile III da Varano
- Camerino
- Italy
| | - Nasuti Cinzia
- Scuola del Farmaco e dei Prodotti della Salute Università di Camerino
- Via Gentile III da Varano
- Camerino
- Italy
| | - Fedeli Donatella
- Scuola del Farmaco e dei Prodotti della Salute Università di Camerino
- Via Gentile III da Varano
- Camerino
- Italy
| | | | | | | |
Collapse
|
|
28
|
Cruz MHC, Leal CLV, Cruz JF, Tan DX, Reiter RJ. Essential actions of melatonin in protecting the ovary from oxidative damage. Theriogenology 2014; 82:925-32. [PMID: 25107629 DOI: 10.1016/j.theriogenology.2014.07.011] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2014] [Revised: 07/02/2014] [Accepted: 07/05/2014] [Indexed: 01/03/2023]
Abstract
Free radicals and other reactive species are involved in normal ovarian physiology. However, they are also highly reactive with complex cellular molecules (proteins, lipids, and DNA) and alter their functions leading to oxidative stress. Oxidative damage may play a prominent role in the development of disorders that considerably influence female fertility. Melatonin, because of its amphiphilic nature that allows for crossing morphophysiological barriers, is an effective antioxidant for protecting macromolecules against oxidative stress caused by reactive species. The balance between reactive oxygen species and antioxidants within the follicle seems to be critical to the function of the oocyte and granulosa cells and evidence has accumulated showing that melatonin is involved in the protection of these cells. Melatonin appears to have varied functions at different stages of follicle development, oocyte maturation, and luteal stage. Melatonin concentration in the growing follicle may be an important factor in avoiding atresia, because melatonin in the follicular fluid reduces apoptosis of critical cells. Melatonin also has protective actions during oocyte maturation reducing intrafollicular oxidative damage. An association between melatonin concentrations in follicular fluid and oocyte quality has been reported; this would allow a preovulatory follicle to fully develop and provide a competent oocyte for fertilization. The functional role of reactive species and the cytoprotective properties of melatonin on the ovary from oxidative damage are summarized in this brief review.
Collapse
Affiliation(s)
- M H C Cruz
- Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, USP, Pirassununga, SP, Brazil.
| | - C L V Leal
- Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, USP, Pirassununga, SP, Brazil
| | - J F Cruz
- Department of Plant Science and Animal Science, Southwest Bahia State University, UESB, Vitória da Conquista, BA, Brazil
| | - D X Tan
- Department of Cellular and Structural Biology, UT Health Science Center at San Antonio, San Antonio, Texas, USA
| | - R J Reiter
- Department of Cellular and Structural Biology, UT Health Science Center at San Antonio, San Antonio, Texas, USA
| |
Collapse
|
|
29
|
Berghella AM, Contasta I, Marulli G, D'Innocenzo C, Garofalo F, Gizzi F, Bartolomucci M, Laglia G, Valeri M, Gizzi M, Friscioni M, Barone M, Del Beato T, Secinaro E, Pellegrini P. Ageing gender-specific "Biomarkers of Homeostasis", to protect ourselves against the diseases of the old age. IMMUNITY & AGEING 2014; 11:3. [PMID: 24498974 PMCID: PMC3923003 DOI: 10.1186/1742-4933-11-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/28/2013] [Accepted: 12/09/2013] [Indexed: 12/17/2022]
Abstract
Low-grade inflammatory state causes the development of the principal chronic-degenerative pathologies related with ageing. Consequently, it is required a better comprehension of the physiologic origins and the consequences of the low-grade inflammatory state for the identification of 1) the basic mechanisms that lead to the chronic inflammatory state and, after that, to the progression toward the pathologies and 2) the parallel identification of the prognostic biomarkers typical of these passages. These biomarkers could bring to several improvements in the health quality, allowing an early diagnosis and more effective treatments for: a) the prevention strategies on the healthy population, to assure a healthy longevity and b) the identification of personalized treatment in patients, to assure the benefit of the therapy. For the identification of these biomarkers it is necessary to consider that the ageing processes produce alterations of the physiologic systems and that these modifications compromise the communications between these networks: this state constitutes an obstacle for an appropriate physiologic homeostasis, that plays a fundamental role for the safeguard of the health. It is also to be considered that immune senescence affects both men and women, but it does it in different ways: a sexual dimorphism of immune pathways in the setting of immune response homeostasis is normally present, as we previously underlined. Therefore we hypothesize that, in order to prevent the development of the chronic-degenerative pathologies related with ageing, it is important to identify "Biomarkers of Homeostasis " specific for each gender: these are biologic molecules that should be measurable in a practical and no-invasive way and whose variations can quantify the male and female risk of losing the physiologic system homeostatic capacity. This competence is not only critical in the control of inflammation, but it is also prognostic for the passages from low-grade inflammatory state to the chronic inflammation and to the progression toward the degenerative pathologies. Beginning from the actual results, our intent is 1) to discuss and underline the importance of these new research perspectives in the definition of ageing gender-specific clinical "Biomarkers of Homeostasis" and 2) to propose homeostasis biomarkers, already present in the research results.
Collapse
Affiliation(s)
- Anna Maria Berghella
- Istituto di Farmacologia Traslazionale (IFT), Consiglio Nazionale delle Ricerche (CNR), Unità Operativa di Supporto (UOS), via G, Carducci, 32 - Rotilio Center, 67100 L'Aquila, Italy.
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
30
|
Differential regulation of the rainbow trout (Oncorhynchus mykiss) MT-A gene by nuclear factor interleukin-6 and activator protein-1. BMC Mol Biol 2013; 14:28. [PMID: 24341438 PMCID: PMC3867414 DOI: 10.1186/1471-2199-14-28] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2013] [Accepted: 12/06/2013] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Previously we have identified a distal region of the rainbow trout (Oncorhynchus mykiss) metallothionein-A (rtMT-A) enhancer region, being essential for free radical activation of the rtMT-A gene. The distal promoter region included four activator protein 1 (AP1) cis-acting elements and a single nuclear factor interleukin-6 (NF-IL6) element. In the present study we used the rainbow trout hepatoma (RTH-149) cell line to further examine the involvement of NF-IL6 and AP1 in rtMT-A gene expression following exposure to oxidative stress and tumour promotion. RESULTS Using enhancer deletion studies we observed strong paraquat (PQ)-induced rtMT-A activation via NF-IL6 while the AP1 cis-elements showed a weak but significant activation. In contrast to mammals the metal responsive elements were not activated by oxidative stress. Electrophoretic mobility shift assay (EMSA) mutation analysis revealed that the two most proximal AP1 elements, AP11,2, exhibited strong binding to the AP1 consensus sequence, while the more distal AP1 elements, AP13,4 were ineffective. Phorbol-12-myristate-13-acetate (PMA), a known tumor promoter, resulted in a robust induction of rtMT-A via the AP1 elements alone. To determine the conservation of regulatory functions we transfected human Hep G2 cells with the rtMT-A enhancer constructs and were able to demonstrate that the cis-elements were functionally conserved. The importance of NF-IL6 in regulation of teleost MT is supported by the conservation of these elements in MT genes from different teleosts. In addition, PMA and PQ injection of rainbow trout resulted in increased hepatic rtMT-A mRNA levels. CONCLUSIONS These studies suggest that AP1 primarily is involved in PMA regulation of the rtMT-A gene while NF-IL6 is involved in free radical regulation. Taken together this study demonstrates the functionality of the NF-IL6 and AP-1 elements and suggests an involvement of MT in protection during pathological processes such as inflammation and cancer.
Collapse
|
|
31
|
Goldstein N, Goldstein R, Terterov D, Kamensky AA, Kovalev GI, Zolotarev YA, Avakyan GN, Terterov S. Blood-brain barrier unlocked. BIOCHEMISTRY (MOSCOW) 2012; 77:419-24. [PMID: 22813582 DOI: 10.1134/s000629791205001x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The brain is protected by a physiological blood-brain barrier (BBB) against toxins and some metabolites circulating in the blood. At the same time, the BBB limits penetration into the brain of many neuroactive drugs. Efficient ways to increase BBB permeability for delivery of drugs of different chemical nature into the brain are unknown. This work deals with delivery into the brain of 10(-2) M dopamine, a substance that does not penetrate the BBB under normal circumstances. It was studied in two independent experiments: (i) penetration of (3)H-labeled dopamine from its mixture with 10(-5) M H2O2 into hypothalamus and striatum structures of intact rat brain, and (ii) effect of unlabeled dopamine from a mixture with H(2)O(2) on the rat motor activity in a haloperidol catalepsy model. It was shown that (i) at the third minute after nasal application of the dopamine + H(2)O(2) mixture, the dopamine level increases 45-fold in the hypothalamus and almost 30-fold in the striatum and (ii) motility of animals in the catalepsy haloperidol model is recovered 90 sec after intranasal introduction of dopamine. No such effects were observed after replacement of H(2)O(2) by 0.9% NaCl solution. Thus, it was shown on the example of dopamine that its introduction into the nasal cavity simultaneously with H(2)O(2) provides for rapid delivery of the drug into the brain. These results expand our knowledge concerning the biological role of exoROS in modulating BBB permeability and may contribute to the development of a new therapeutic strategy for neurological diseases.
Collapse
Affiliation(s)
- N Goldstein
- Department of Human and Animal Physiology, Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia.
| | | | | | | | | | | | | | | |
Collapse
|
|
32
|
Alvarez GM, Dalvit GC, Cetica PD. Influence of the Cumulus and Gonadotropins on the Metabolic Profile of Porcine Cumulus-Oocyte Complexes During In Vitro Maturation. Reprod Domest Anim 2012; 47:856-64. [DOI: 10.1111/j.1439-0531.2011.01943.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
|
|
33
|
Mouse hematopoietic cell-targeted STAT3 deletion: stem/progenitor cell defects, mitochondrial dysfunction, ROS overproduction, and a rapid aging-like phenotype. Blood 2012; 120:2589-99. [PMID: 22665934 DOI: 10.1182/blood-2012-01-404004] [Citation(s) in RCA: 112] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Nuclear transcription factor Stat3 is important for proper regulation of hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) proliferation, survival, and cytokine signaling responses. A new, noncanonical role for Stat3 in mitochondrial function has been discovered recently. However, there is little information on the role(s) of mitochondrial Stat3 in HSC/HPC function, especially potential effects of Stat3/mitochondrial dysregulation in human diseases. We investigated hematopoietic cell-targeted deletion of the STAT3 gene in HSCs/HPCs with a focus on mitochondrial function. We found that STAT3(-/-) mice, which have a very shortened lifespan, dysfunctional/dysregulated mitochondrial function and excessive reactive oxygen species production in HSCs/HPCs that coincides with pronounced defects in function. These animals have a blood phenotype with similarities to premature aging and to human diseases of myelodysplastic syndrome and myeloproliferative neoplasms such as erythroid dysplasia, anemia, excessive myeloproliferation, and lymphomyeloid ratio shifts. We show herein that the lifespan of STAT3(-/-) animals is lengthened by treatment with a reactive oxygen species scavenger, which lessened the severity of the blood phenotype. These data suggest a need for more detailed studies of role(s) of Stat3 in HSC/HPC mitochondrial function in human diseases and raise the idea that mitochondrial Stat3 could be used as a potential therapeutic target.
Collapse
|
|
34
|
Talebi A, Zavareh S, Kashani MH, Lashgarbluki T, Karimi I. The effect of alpha lipoic acid on the developmental competence of mouse isolated preantral follicles. J Assist Reprod Genet 2012; 29:175-83. [PMID: 22231012 PMCID: PMC3270132 DOI: 10.1007/s10815-011-9706-6] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2011] [Accepted: 12/27/2011] [Indexed: 10/14/2022] Open
Abstract
PURPOSE This study was designed to investigate the effect of alpha-lipoic acid (ALA) on reactive oxygen species (ROS) production, total antioxidant capacity (TAC) and developmental competence of cultured pre-antral follicles derived from mouse ovarian tissue. METHODS Pre-antral follicles were isolated from immature mouse ovaries and were cultured in α- minimal essential medium supplemented with different concentrations (0, 50, 100, 250 and 500 uM) of ALA. Follicular growth, oocyte maturation and embryo development were evaluated. Separately, ROS and TAC were measured after 0, 24, 48, 72 and 96 h of culture with spectrofluorometery and ferric reducing/antioxidant power (FRAP) assay, respectively. RESULTS In the presence of 100 uM ALA, developmental rates of follicles, oocytes and embryos were significantly higher than other groups (p < 0.05). At 96 h after culture, a decrease in ROS and an increase in TAC were observed in ALA group compared to control group (p < 0.05). CONCLUSION ALA (100 uM) improves the in vitro development of follicles. This effect may be mediated by decreasing ROS concentration and increasing follicular TAC level during the culture period.
Collapse
Affiliation(s)
- Ali Talebi
- School of Biology, Damghan University, Damghan, Iran
| | - Saeed Zavareh
- School of Biology, Damghan University, Damghan, Iran
| | | | | | - Isaac Karimi
- School of Veterinary medicine, Razi University, Kermanshah, Iran
| |
Collapse
|
|
35
|
Simate GS, Iyuke SE, Ndlovu S, Heydenrych M, Walubita LF. Human health effects of residual carbon nanotubes and traditional water treatment chemicals in drinking water. ENVIRONMENT INTERNATIONAL 2012; 39:38-49. [PMID: 22208741 DOI: 10.1016/j.envint.2011.09.006] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/07/2011] [Revised: 09/05/2011] [Accepted: 09/14/2011] [Indexed: 05/19/2023]
Abstract
The volume of industrial and domestic wastewater is increasing significantly year by year with the change in the lifestyle based on mass consumption and mass disposal brought about by the dramatic development of economies and industries. Therefore, effective advanced wastewater treatment is required because wastewater contains a variety of constituents such as particles, organic materials, and emulsion depending on the resource. However, residual chemicals that remain during the treatment of wastewaters form a variety of known and unknown by-products through reactions between the chemicals and some pollutants. Chronic exposure to these by-products or residual chemicals through the ingestion of drinking water, inhalation and dermal contact during regular indoor activities (e.g., showering, bathing, cooking) may pose cancer and non-cancer risks to human health. For example, residual aluminium salts in treated water may cause Alzheimer's disease (AD). As for carbon nanotubes (CNTs), despite their potential impacts on human health and the environment having been receiving more and more attention in the recent past, existing information on the toxicity of CNTs in drinking water is limited with many open questions. Furthermore, though general topics on the human health impacts of traditional water treatment chemicals have been studied, no comparative analysis has been done. Therefore, a qualitative comparison of the human health effects of both residual CNTs and traditional water treatment chemicals is given in this paper. In addition, it is also important to cover and compare the human health effects of CNTs to those of traditional water treatment chemicals together in one review because they are both used for water treatment and purification.
Collapse
Affiliation(s)
- Geoffrey S Simate
- School of Chemical and Metallurgical Engineering, University of the Witwatersrand, Johannesburg, P/Bag 3, Wits 2050, South Africa.
| | | | | | | | | |
Collapse
|
|
36
|
Breitenbach M, Laun P, Dickinson JR, Klocker A, Rinnerthaler M, Dawes IW, Aung-Htut MT, Breitenbach-Koller L, Caballero A, Nyström T, Büttner S, Eisenberg T, Madeo F, Ralser M. The role of mitochondria in the aging processes of yeast. Subcell Biochem 2012; 57:55-78. [PMID: 22094417 DOI: 10.1007/978-94-007-2561-4_3] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
This chapter reviews the role of mitochondria and of mitochondrial metabolism in the aging processes of yeast and the existing evidence for the "mitochondrial theory of aging mitochondrial theory of aging ". Mitochondria are the major source of ATP in the eukaryotic cell but are also a major source of reactive oxygen species reactive oxygen species (ROS) and play an important role in the process of apoptosis and aging. We are discussing the mitochondrial theory of aging mitochondrial theory of aging (TOA), its origin, similarity with other TOAs, and its ramifications which developed in recent decades. The emphasis is on mother cell-specific aging mother cell-specific aging and the RLS (replicative lifespan) with only a short treatment of CLS (chronological lifespan). Both of these aging processes may be relevant to understand also the aging of higher organisms, but they are biochemically very different, as shown by the fact the replicative aging occurs on rich media and is a defect in the replicative capacity of mother cells, while chronological aging occurs in postmitotic cells that are under starvation conditions in stationary phase leading to loss of viability, as discussed elsewhere in this book. In so doing we also give an overview of the similarities and dissimilarities of the various aging processes of the most often used model organisms for aging research with respect to the mitochondrial theory of aging mitochondrial theory of aging.
Collapse
Affiliation(s)
- Michael Breitenbach
- Division of Genetics, Department of Cell Biology, University of Salzburg, Salzburg, Austria,
| | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
37
|
Whitaker BD, Casey SJ, Taupier R. The effects of N-acetyl-L-cysteine supplementation on in vitro porcine oocyte maturation and subsequent fertilisation and embryonic development. Reprod Fertil Dev 2012; 24:1048-54. [DOI: 10.1071/rd12002] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2011] [Accepted: 03/07/2012] [Indexed: 01/21/2023] Open
Abstract
The effects of supplementation with 1.5 mM n-acetyl-l-cysteine (NAC) during in vitro oocyte maturation were studied. Oocytes were supplemented with 1.5 mM NAC during maturation for 0 to 24 h, 24 to 48 h, or 0 to 48 h then subjected to IVF and embryo development. Oocytes were evaluated after maturation for intracellular glutathione concentration, superoxide dismutase and glutathione peroxidase activities and DNA fragmentation. Fertilisation and embryonic development success were also evaluated. There was no effect of treatment on intracellular glutathione concentrations, enzyme activities or fertilisation success rates. Supplementing NAC during maturation significantly decreased (P < 0.05) the percentage of oocytes with fragmented DNA compared with no NAC supplementation. Supplementing NAC from 24 to 48 h or 0 to 48 h resulted in a significantly higher (P < 0.05) percentage of oocytes with male pronuclei than for oocytes from the other treatment groups. There was no difference in the percentage of embryos cleaved by 48 h after IVF between treatment groups. Supplementing NAC from 24 to 48 h or 0 to 48 h resulted in a significantly higher (P < 0.05) percentage of embryos reaching the blastocyst stage by 144 h after IVF compared with the other treatment groups. These results indicate that supplementation of the oocyte maturation medium with 1.5 mM NAC, specifically during the last 24 h, improves male pronucleus formation and blastocyst development in pigs.
Collapse
|
|
38
|
Abstract
Male factor accounts for almost 50% cases of infertility. The exact mechanism of sperm dysfunction is not known in many cases. Extensive research in the last decade has led to the identification of free radicals (reactive oxygen species) as mediators of sperm dysfunction in both specific diagnoses and idiopathic cases of male infertility. Elevated levels of reactive oxygen species are seen in up to 30-80% of men with male infertility. The role of free radicals has been studied extensively in the process of human reproduction. We know now that a certain level of free radicals is necessary for normal sperm function, whereas an excessive level of free radicals can cause detrimental effect on sperm function and subsequent fertilisation and offspring health. Oxidative stress develops when there is an imbalance between generation of free radicals and scavenging capacity of anti-oxidants in reproductive tract. Oxidative stress has been shown to affect both standard semen parameters and fertilising capacity. In addition, high levels of free radicals have been associated with lack of or poor fertility outcome after natural conception or assisted reproduction. Diagnostic techniques to quantify free radicals in infertile patients can assist physicians treating patients with infertility to plan for proper treatment strategies. In vivo anti-oxidants can be used against oxidative stress in male reproductive tract. Supplementation of in vitro anti-oxidants can help prevent the oxidative stress during sperm preparation techniques in assisted reproduction.
Collapse
Affiliation(s)
- Ashok Agarwal
- Centre for Advanced Research in Human, Reproduction, Infertility, and Sexual Function, Glickman Urological Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Desk A19.1, Cleveland, OH 44195, USA.
| | | |
Collapse
|
|
39
|
Sasaki M, Joh T. Oxidative stress and ischemia-reperfusion injury in gastrointestinal tract and antioxidant, protective agents. J Clin Biochem Nutr 2011; 40:1-12. [PMID: 18437208 PMCID: PMC2291499 DOI: 10.3164/jcbn.40.1] [Citation(s) in RCA: 127] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2006] [Accepted: 07/07/2006] [Indexed: 12/14/2022] Open
Abstract
Exacerbation of hypoxic injury after reoxygenation is a crucial mechanism mediating organ injury in transplantation, and in myocardial, hepatic, gastrointestinal, cerebral, renal, and other ischemic syndromes. The occlusion and reperfusion of the splanchnic artery is a useful animal model to elucidate the mechanism of gastrointestinal injury induced by ischemia-reperfusion (I/R). Although xanthine oxidase is a major source of reactive oxygen species (ROS), which plays an important role in the I/R-induced intestinal injury, there are many other sources of intracellular ROS. Various treatment modalities have been successfully applied to attenuate the I/R injury in animal models. This review focuses on the role of oxidant stress in the mechanism of I/R injury and the use of antioxidant agents for its treatment.
Collapse
Affiliation(s)
- Makoto Sasaki
- Internal Medicine and Bioregulation, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho, Nagoya City 467-8601, Japan
| | | |
Collapse
|
|
40
|
Galli C, Passeri G, Macaluso GM. FoxOs, Wnts and oxidative stress-induced bone loss: new players in the periodontitis arena? J Periodontal Res 2011; 46:397-406. [PMID: 21332475 DOI: 10.1111/j.1600-0765.2011.01354.x] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND OBJECTIVE Chronic periodontitis is a widespread disease affecting tooth-supporting structures that can lead to extensive loss of periodontal ligament and bone, ultimately resulting in tooth loss. Extensive evidence has demonstrated a strong association between age, metabolic disorders such as type II diabetes, oxidative stress and alveolar bone loss. The molecular players controlling bone maintenance and underlying age-related bone loss and its links to the general metabolism are currently the object of intense research. MATERIAL AND METHODS Recent findings are summarized to elucidate the molecular mechanisms linking oxidative stress, bone loss and metabolic factors. RESULTS It is well known that reactive oxygen species are an inevitable consequence of cellular respiration and that organisms have developed an efficient array of defenses against them. The core of this complex defense line is a family of transcription factors, known as FoxOs, which can bind to β-catenin and initiate a transcriptional programme regulating cell apoptosis, DNA repair and degradation of reactive oxygen species. An increase in reactive oxygen species due, for example, to age or insulin resistance, generates a situation in which bone formation is impaired by activation of FoxO, and a decrease in Wnt signaling and bone resorption are promoted. CONCLUSION The balance between FoxO and the Wnt pathway is finely tuned by systemic and local factors, creating a far-reaching mechanism that dictates the fate of mesenchymal progenitors and regulates the homeostasis of bone, providing a rationale for the impairment of systemic and alveolar bone maintenance clinically observed with age and metabolic diseases.
Collapse
Affiliation(s)
- C Galli
- Department of Internal Medicine Unit of Periodontology, University of Parma, Parma, Italy.
| | | | | |
Collapse
|
|
41
|
Varghese AC, Ly KD, Corbin C, Mendiola J, Agarwal A. Oocyte developmental competence and embryo development: impact of lifestyle and environmental risk factors. Reprod Biomed Online 2010; 22:410-20. [PMID: 21388885 DOI: 10.1016/j.rbmo.2010.11.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2010] [Revised: 10/19/2010] [Accepted: 11/10/2010] [Indexed: 11/24/2022]
Abstract
Oocyte development is the end result of a sophisticated biological process that is hormonally regulated and produced by highly specialized cellular lines that differentiate in early embryo/fetal development. Embryo development is initially regulated by maternal transcripts until replaced by embryonic genomic expression. Then, an assortment of hormones and local environmental factors in various concentrations along the reproductive tract (e.g. fallopian tube, endometrial lining) provide the protection, nutrients and means of communication for the embryo to implant and develop. Both oocytes and embryos are susceptible to environmental, occupational and lifestyle exposures that can exert direct toxic effects and disrupt hormones. While some exposures may produce reversible changes, others, especially those damaging germinal cells in utero or during prepuberty, may result in permanent sequelae that continue in future generations. This article reviews the main factors that affect female fertility and their possible influence on human reproduction. Some lifestyles, xeno-oestrogens and heavy metals are already known to compromise female reproductive function. Nonetheless, many questions remain and little is known about the effect of many other factors on female fertility.
Collapse
Affiliation(s)
- Alex C Varghese
- Fertility Clinic and IVF Department, AMRI Medical Centre, Kolkata, India
| | - Kim D Ly
- Center for Reproductive Medicine, Glickman Urological and Kidney Institute and Obstetrics and Gynecology and Women's Health Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Cresandra Corbin
- Center for Reproductive Medicine, Glickman Urological and Kidney Institute and Obstetrics and Gynecology and Women's Health Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Jaime Mendiola
- Public Health and Epidemiology Research Group, School of Medicine, University of Murcia, Murcia, Spain
| | - Ashok Agarwal
- Center for Reproductive Medicine, Glickman Urological and Kidney Institute and Obstetrics and Gynecology and Women's Health Institute, Cleveland Clinic, Cleveland, OH, USA
| |
Collapse
|
|
42
|
Mozaffarieh M, Konieczka K, Hauenstein D, Schoetzau A, Flammer J. Half a pack of cigarettes a day more than doubles DNA breaks in circulating leukocytes. Tob Induc Dis 2010; 8:14. [PMID: 21083877 PMCID: PMC2996352 DOI: 10.1186/1617-9625-8-14] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2010] [Accepted: 11/17/2010] [Indexed: 11/10/2022] Open
Abstract
Background The mechanisms by which smoking induces damage is not known for all diseases. One mechanism believed to play a role is oxidative stress. Oxidative stress leads to cellular damage including DNA damage, particularly DNA breaks. We conducted this study to test the hypothesis that smokers have increased DNA breaks in their circulating leukocytes. Methods A comparative quantification of single-stranded DNA breaks was performed by comet assay analysis in the circulating leukocytes of ten healthy smokers (average smoking rate: half a pack a day, range: 9-12 cigarettes a day) and ten age and sex matched healthy non-smokers. DNA breaks lead to smaller pieces of DNA, which migrate out of the nucleus forming a tail during gel-electrophoresis. Damage of an individual cell was quantified by the parameters tail moment and olive moment. Results Smoking had a clear effect on both study parameters (tail and olive moment). Smokers had more than double the amount of ss-DNA breaks in their circulating leukocytes than non-smokers [tail moment: 0·75 AU [smokers] compared to 0·2 AU [non-smokers]; olive moment: 0·85 AU [smokers] compared to 0·3 AU [non-smokers]; both p < 0·001]. Conclusion Smoking half a pack a day interferes with DNA integrity. One potential explanation for the enhanced DNA breaks in smokers is oxidative stress.
Collapse
Affiliation(s)
- Maneli Mozaffarieh
- Department of Ophthalmology, University of Basel, Mittlere Strasse 91, CH-4031 Basel, Switzerland.
| | | | | | | | | |
Collapse
|
|
43
|
Vossen E, Ntawubizi M, Raes K, Smet K, Huyghebaert G, Arnouts S, De Smet S. Effect of dietary antioxidant supplementation on the oxidative status of plasma in broilers. J Anim Physiol Anim Nutr (Berl) 2010; 95:198-205. [DOI: 10.1111/j.1439-0396.2010.01041.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
|
|
44
|
Costenbader KH, Kang JH, Karlson EW. Antioxidant intake and risks of rheumatoid arthritis and systemic lupus erythematosus in women. Am J Epidemiol 2010; 172:205-16. [PMID: 20534819 DOI: 10.1093/aje/kwq089] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Antioxidants may protect against development of rheumatoid arthritis or systemic lupus erythematosus by combating oxidative stress. The authors identified and confirmed incident cases of rheumatoid arthritis and systemic lupus erythematosus among 184,643 US women followed in the Nurses' Health Study and Nurses' Health Study II cohorts in 1980-2004. Semiquantitative food frequency questionnaires assessed intakes of vitamins A, C, and E and alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein, and zeaxanthin from foods and supplements. The authors examined total antioxidant intake by calculating a "ferric-reducing ability of plasma" score, a new method for quantifying the total antioxidant effect of a food based on the reduction of ferric to ferrous iron by antioxidants. Cumulative updated total energy-adjusted dietary intakes were used. Associations between intake of each nutrient and incident rheumatoid arthritis and systemic lupus erythematosus were examined in age-adjusted and Cox proportional hazards models, adjusted for confounders. Results from the cohorts were pooled meta-analytically by using random-effects models. The authors identified 787 incident rheumatoid arthritis cases and 192 systemic lupus erythematosus cases for whom prospective dietary information was available. In these large, prospective cohorts of women, antioxidant intake was not associated with the risk of developing either rheumatoid arthritis or systemic lupus erythematosus.
Collapse
Affiliation(s)
- Karen H Costenbader
- Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
| | | | | |
Collapse
|
|
45
|
Wang ZH, Ah Kang K, Zhang R, Piao MJ, Jo SH, Kim JS, Kang SS, Lee JS, Park DH, Hyun JW. Myricetin suppresses oxidative stress-induced cell damage via both direct and indirect antioxidant action. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2010; 29:12-8. [PMID: 21787576 DOI: 10.1016/j.etap.2009.08.007] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/10/2009] [Revised: 08/13/2009] [Accepted: 08/31/2009] [Indexed: 05/05/2023]
Abstract
We evaluated the cytoprotective effect of myricetin on oxidative stress damaged cells by assessment of the scavenging effect of reactive oxygen species (ROS) and the activities of antioxidant enzymes. Myricetin showed the scavenging effect of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals on intracellular ROS. In addition, myricetin restored the activity and protein expression of cellular antioxidant defense enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) reduced by hydrogen peroxide (H(2)O(2)) treatment. H(2)O(2)-induced cellular DNA and lipid damages, and myricetin was found to prevent the DNA damage shown by inhibition of DNA tail and it decreased nuclear phospho-histone H2A.X expression, which are both markers for DNA strand breakage. Membrane lipid peroxidation was also attenuated as shown by inhibition of TBARS formation and of fluorescence intensity of diphenyl-1-pyrenylphosphine (DPPP). These results suggest that myricetin protects cells against H(2)O(2)-induced cell damage via inhibition of ROS generation and activation of antioxidant enzymes.
Collapse
Affiliation(s)
- Zhi Hong Wang
- School of Medicine, Jeju National University, Jeju-si 690-756, Republic of Korea
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
46
|
Zaidi A, Fernandes D, Bean JL, Michaelis ML. Effects of paraquat-induced oxidative stress on the neuronal plasma membrane Ca(2+)-ATPase. Free Radic Biol Med 2009; 47:1507-14. [PMID: 19715754 PMCID: PMC2789485 DOI: 10.1016/j.freeradbiomed.2009.08.018] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2009] [Revised: 08/17/2009] [Accepted: 08/20/2009] [Indexed: 12/25/2022]
Abstract
Oxidative stress leads to the disruption of calcium homeostasis in brain neurons; however, the direct effects of oxidants on proteins that regulate intracellular calcium ([Ca(2+)](i)) are not known. The calmodulin (CaM)-stimulated plasma membrane Ca(2+)-ATPase (PMCA) plays a critical role in regulating [Ca(2+)](i). Our previous in vitro studies showed that PMCA present in brain synaptic membranes is readily inactivated by a variety of reactive oxygen species (ROS). The present studies were conducted to determine the vulnerability of PMCA to ROS generated in neurons as would probably occur in vivo. Primary cortical neurons were exposed to paraquat (PQ), a redox cycling agent that generates intracellular ROS. Low concentrations of PQ (5-10 microM) increased PMCA basal activity by two-fold but abolished its sensitivity to CaM. Higher concentrations (25-100 microM) inhibited both components of PMCA activity. Immunoblots showed the formation of high-molecular-weight PMCA aggregates. Additionally, PMCA showed evidence of proteolytic degradation. PMCA proteolysis was prevented by a calpain inhibitor, suggesting a role for calpain. Our findings suggest that PMCA is a sensitive target of oxidative stress in primary neurons. Inactivation of this Ca(2+) transporter under prolonged oxidative stress could alter neuronal Ca(2+) signaling.
Collapse
Affiliation(s)
- Asma Zaidi
- Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS 66045, USA.
| | | | | | | |
Collapse
|
|
47
|
Abstract
AbstractMale Wistar rats were subjected to chronic nicotine treatment (0.3 mg/kg; 7 continuous days) and their memory performance was studied by means of Y-maze and multi-trial passive avoidance tasks. Nicotine significantly decreased spontaneous alternation in Y-maze task and step-through-latency in the multi-trial passive avoidance task, suggesting effects on both short-term memory and long-term memory, respectively. In addition, nicotine induced neuronal apoptosis, DNA fragmentation, reduced antioxidant enzymes activity, and increased production of lipid peroxidation and reactive oxygen species, suggesting pro-oxidant activity. Our results provide further support that nicotine-induced memory impairment is due to an increase in brain oxidative stress in rats.
Collapse
|
|
48
|
Gius D, Mattson D, Bradbury CM, Smart DK, Spitz DR. Thermal stress and the disruption of redox-sensitive signalling and transcription factor activation: possible role in radiosensitization. Int J Hyperthermia 2009; 20:213-23. [PMID: 15195515 DOI: 10.1080/02656730310001619505] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
Abstract
In spite of ongoing research efforts, the specific mechanism(s) of heat-induced alterations in the cellular response to ionizing radiation (IR) remain ambiguous, in part because they likely involve multiple mechanisms and potential targets. One such group of potential targets includes a class of cytoplasmic signalling and/or nuclear transcription factors known as immediate early response genes, which have been suggested to perform cytotoxic as well as cytoprotective roles during cancer therapy. One established mechanism regulating the activity of these early response elements involves changes in cellular oxidation/reduction (redox) status. After establishing common alterations in early response genes by oxidative stress and heat exposure, one could infer that heat shock may have similarities to other forms of environmental antagonists that induce oxidative stress. In this review, recent evidence supporting a mechanistic link between heat shock and oxidative stress will be summarized. In addition, the hypothesis that one mechanism whereby heat shock alters cellular responses to anticancer agents (including hyperthermic radiosensitization) is through heat-induced disruption of redox-sensitive signalling factors will be discussed.
Collapse
Affiliation(s)
- D Gius
- Molecular Radiation Oncology Section, Radiation Oncology Branch, Radiation Oncology Sciences Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
| | | | | | | | | |
Collapse
|
|
49
|
Melatonin and the ovary: physiological and pathophysiological implications. Fertil Steril 2009; 92:328-43. [DOI: 10.1016/j.fertnstert.2008.05.016] [Citation(s) in RCA: 310] [Impact Index Per Article: 19.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2008] [Revised: 05/02/2008] [Accepted: 05/05/2008] [Indexed: 10/21/2022]
|
|
50
|
Avdagić N, Cosović E, Nakas-Ićindić E, Mornjaković Z, Zaciragić A, Hadzović-Dzuvo A. Spirulina platensis protects against renal injury in rats with gentamicin-induced acute tubular necrosis. Bosn J Basic Med Sci 2009; 8:331-6. [PMID: 19125703 DOI: 10.17305/bjbms.2008.2892] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
The present study was carried out to evaluate the renoprotective antioxidant effect of Spirulina platensis on gentamicin-induced acute tubular necrosis in rats. Albino-Wistar rats, (9male and 9 female), weighing approximately 250 g, were used for this study. Rats were randomly assigned to three equal groups. Control group received 0,9 % sodium chloride intraperitoneally for 7 days at the same volume as gentamicin group. Gentamicin group was treated intraperitoneally with gentamicin, 80 mg/kg daily for 7 days. Gentamicin+spirulina group received Spirulina platensis 1000 mg/kg orally 2 days before and 7 days concurrently with gentamicin (80 mg/kg i.p.). Nephrotoxicity was assessed by measuring plasma nitrite concentration, stabile metabolic product of nitric oxide with oxygen. Plasma nitrite concentration was determined by colorimetric method using Griess reaction. For histological analysis kidney specimens were stained with hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) stain. Plasma nitrite concentration and the level of kidney damage were significantly higher in gentamicin group in comparison both to the control and gentamicin+spirulina group. Spirulina platensis significantly lowered the plasma nitrite level and attenuated histomorphological changes related to renal injury caused by gentamicin. Thus, the results from present study suggest that Spirulina platensis has renoprotective potential in gentamicin-induced acute tubular necrosis possibly due to its antioxidant properties.
Collapse
Affiliation(s)
- Nesina Avdagić
- Faculty of Medicine, Institute of Physiology and Biochemistry, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | | | | | | | | | | |
Collapse
|