title: Resveratrol protects the ovary against chromium-toxicity by enhancing endogenous antioxidant enzymes and inhibiting metabolic clearance of estradiol.
abstract: Resveratrol (RVT), a polyphenolic component in grapes and red wine, has been known for its cytoprotective actions against several diseases. However, beneficial effects of RVT against early exposure to endocrine disrupting chemicals (EDCs) have not been understood. EDCs are linked to several ovarian diseases such as premature ovarian failure, polycystic ovary syndrome, early menopause and infertility in women. Hexavalent chromium (CrVI) is a heavy metal EDC, and widely used in >50 industries. Environmental contamination with CrVI in the US is rapidly increasing, predisposing the human to several illnesses including cancers and still birth. Our lab has been involved in determining the molecular mechanism of CrVI-induced female infertility and intervention strategies to mitigate CrVI effects. Lactating mother rats were exposed to CrVI (50ppm potassium dichromate) from postpartum days 1-21 through drinking water with or without RVT (10mg/kg body wt., through oral gavage daily). During this time, F1 females received respective treatments through mother's milk. On postnatal day (PND) 25, blood and the ovary, kidney and liver were collected from the F1 females for analyses. CrVI increased atresia of follicles by increasing cytochrome C and cleaved caspase-3; decreasing antiapoptotic proteins; decreasing estradiol (E2) biosynthesis and enhancing metabolic clearance of E2, increasing oxidative stress and decreasing endogenous antioxidants. RVT mitigated the effects of CrVI by upregulating cell survival proteins and AOXs; and restored E2 levels by inhibiting hydroxylation, glucuronidation and sulphation of E2. This is the first study to report the protective effects of RVT against any toxicant in the ovary.
authors.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA. Electronic address: skbanu@cvm.tamu.edu.
authors.forename: Sakhila K
authors.initials: SK
authors.lastname: Banu
authors.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Jone A
authors.initials: JA
authors.lastname: Stanley
authors.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Kirthiram K
authors.initials: KK
authors.lastname: Sivakumar
authors.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Joe A
authors.initials: JA
authors.lastname: Arosh
authors.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Burghardt
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity; D002374:Catalase / Q000378:metabolism; D002857:Chromium / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity; D004958:Estradiol / Q000097:blood / Q000378:metabolism; D005260:Female; D005496:Follicular Atresia / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects / Q000473:pathology; D010053:Ovary / Q000187:drug effects* / Q000473:pathology; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013739:Testosterone / Q000097:blood
chemical_list: D002273:Carcinogens; D004785:Environmental Pollutants; D020011:Protective Agents; D017382:Reactive Oxygen Species; D013267:Stilbenes; D002857:Chromium; C074702:chromium hexavalent ion; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000077185:Resveratrol
keywords: Antioxidants; Chromium; Ovary; Oxidative Stress; Resveratrol; Steroidogenesis