دورية أكاديمية
Methoxychlor causes mitochondrial dysfunction and oxidative damage in the mouse ovary.
| العنوان: | Methoxychlor causes mitochondrial dysfunction and oxidative damage in the mouse ovary. |
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| المؤلفون: | Gupta RK; Program in Toxicology, Department of Epidemiology and Preventive Medicine, University of Maryland, 660 W. Redwood Street, Howard Hall 133B, Baltimore, MD, USA., Schuh RA, Fiskum G, Flaws JA |
| المصدر: | Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2006 Nov 01; Vol. 216 (3), pp. 436-45. Date of Electronic Publication: 2006 Jul 01. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Academic Press Country of Publication: United States NLM ID: 0416575 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0041-008X (Print) Linking ISSN: 0041008X NLM ISO Abbreviation: Toxicol Appl Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York, NY : Academic Press Original Publication: New York. |
| مواضيع طبية MeSH: | Insecticides/*toxicity , Methoxychlor/*toxicity , Mitochondria/*drug effects , Ovarian Diseases/*metabolism , Oxidative Stress/*drug effects, 8-Hydroxy-2'-Deoxyguanosine ; Animals ; Catalase/biosynthesis ; Deoxyguanosine/analogs & derivatives ; Deoxyguanosine/metabolism ; Female ; Glutathione/metabolism ; Glutathione Peroxidase/biosynthesis ; Hydrogen Peroxide/metabolism ; Immunohistochemistry ; Mice ; Mitochondria/metabolism ; Ovarian Diseases/chemically induced ; Ovarian Diseases/enzymology ; Ovary/drug effects ; Ovary/enzymology ; Ovary/metabolism ; Oxidants/metabolism ; Oxygen Consumption/drug effects ; RNA/biosynthesis ; Reactive Oxygen Species/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Superoxide Dismutase/biosynthesis ; Superoxide Dismutase-1 ; Tyrosine/analogs & derivatives ; Tyrosine/metabolism |
| مستخلص: | Methoxychlor (MXC) is an organochlorine pesticide that reduces fertility in female rodents by causing ovarian atrophy, persistent estrous cyclicity, and antral follicle atresia (apoptotic cell death). Oxidative damage resulting from reactive oxygen species (ROS) generation has been demonstrated to lead to toxicant-induced cell death. Thus, this work tested the hypothesis that MXC causes oxidative damage to the mouse ovary and affects mitochondrial respiration in a manner that stimulates ROS production. For the in vitro experiments, mitochondria were collected from adult cycling mouse ovaries, treated with vehicle (dimethyl sulfoxide; DMSO) or MXC, and subjected to polarographic measurements of respiration. For the in vivo experiments, adult cycling CD-1 mice were dosed with either vehicle (sesame oil) or MXC for 20 days. After treatment, ovarian mitochondria were isolated and subjected to measurements of respiration and fluorimetric measurements of H2O2 production. Some ovaries were also fixed and processed for immunohistochemistry using antibodies for ROS production markers: nitrotyrosine and 8-hydroxy-2'-deoxyguanosine (8-OHG). Ovaries from in vivo experiments were also used to measure the mRNA expression and activity of antioxidants such as Cu/Zn superoxide dismutase (SOD1), glutathione peroxidase (GPX), and catalase (CAT). The results indicate that MXC significantly impairs mitochondrial respiration, increases production of H2O2, causes more staining for nitrotyrosine and 8-OHG in antral follicles, and decreases the expression and activity of SOD1, GPX, and CAT as compared to controls. Collectively, these data indicate that MXC inhibits mitochondrial respiration, causes ROS production, and decreases antioxidant expression and activity in the ovary, specifically in the antral follicles. Therefore, it is possible that MXC causes atresia of ovarian antral follicles by inducing oxidative stress through mitochondrial production of ROS. |
| معلومات مُعتمدة: | R01 ES012893-01A2 United States ES NIEHS NIH HHS |
| المشرفين على المادة: | 0 (Insecticides) 0 (Oxidants) 0 (Reactive Oxygen Species) 3604-79-3 (3-nitrotyrosine) 42HK56048U (Tyrosine) 63231-63-0 (RNA) 88847-89-6 (8-Hydroxy-2'-Deoxyguanosine) BBX060AN9V (Hydrogen Peroxide) EC 1.11.1.6 (Catalase) EC 1.11.1.9 (Glutathione Peroxidase) EC 1.15.1.1 (Sod1 protein, mouse) EC 1.15.1.1 (Superoxide Dismutase) EC 1.15.1.1 (Superoxide Dismutase-1) G9481N71RO (Deoxyguanosine) GAN16C9B8O (Glutathione) RIA79UD69L (Methoxychlor) |
| تواريخ الأحداث: | Date Created: 20060808 Date Completed: 20061206 Latest Revision: 20191210 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.taap.2006.06.013 |
| PMID: | 16890261 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 0041-008X |
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| DOI: | 10.1016/j.taap.2006.06.013 |