title: Molecular mechanisms of a novel selenium-based complementary medicine which confers protection against hyperandrogenism-induced polycystic ovary.
abstract: The objective was to evaluate ovarian functionality and oxidative response in hyperandrogenism-induced polycystic ovary (PCO) and the protective effects of immunomodulator drug (IMOD), an electromagnetically-treated, selenium-based, herbal medicine. Daily oral administration of letrozole (1 mg/kg) for 21 consecutive days induced ovarian cysts in female rats. An effective dose of IMOD (30 mg/kg per day) was given intraperitoneally for 21 days. Biomarkers of ovarian function, serum concentrations of estradiol, progesterone, testosterone, and ovarian prostaglandin-E (PGE), were analyzed. To determine the role of oxidative stress (OS) in hyperandrogenism-induced PCO, concentrations of cellular lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), peroxynitrite (ONOO), and tumor necrosis factor (TNF)-α as a marker of inflammation and apoptosis were measured in serum and ovaries. Letrozole-induced PCO resulted in significant increases in concentrations of lipid peroxidation and peroxynitrite in serum and ovary, but significantly decreased superoxide dismutase, catalase, and glutathione peroxidase. Serum concentrations of testosterone and TNF-α, and ovarian prostaglandin-E were increased (P < 0.001) in animals with cysts versus control, whereas estradiol and progesterone were decreased (P < 0.01 and P < 0.001, respectively). When compared with controls, letrozole induced irregular cycles and PCO characterized by a high incidence of subcapsular ovarian cysts with a diminished granulosa cell layer, luteinized granulosa cells in the cyst wall, significantly more atretic preantral and antral follicles, and absence of CL. There were almost no intact primary, secondary, and tertiary follicles in PCO rats. All end points assessed were significantly improved by IMOD and reached close to normal levels. In conclusion, the present study provided evidence that toxic free radicals and TNF-α were involved in the pathogenesis of PCO; furthermore, IMOD prevented ovarian histopathologic, endocrine, and biochemical alterations induced by hyperandrogenism.
authors.affiliation: Laboratory of Toxicology, Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: M A
authors.initials: MA
authors.lastname: Rezvanfar
authors.forename: M A
authors.initials: MA
authors.lastname: Rezvanfar
authors.forename: A
authors.initials: A
authors.lastname: Ahmadi
authors.forename: H A
authors.initials: HA
authors.lastname: Shojaei-Saadi
authors.forename: M
authors.initials: M
authors.lastname: Baeeri
authors.forename: M
authors.initials: M
authors.lastname: Abdollahi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D004958:Estradiol / Q000097:blood; D005260:Female; D017588:Hyperandrogenism / Q000139:chemically induced / Q000150:complications*; D000077289:Letrozole; D015227:Lipid Peroxidation / Q000187:drug effects; D009570:Nitriles / Q000008:administration & dosage; D010053:Ovary / Q000737:chemistry; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage*; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control*; D011374:Progesterone / Q000097:blood; D011458:Prostaglandins E / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000008:administration & dosage*; D013739:Testosterone / Q000097:blood; D014230:Triazoles / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D009570:Nitriles; D010936:Plant Extracts; D011458:Prostaglandins E; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; C555145:setarud; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D000077289:Letrozole; D012643:Selenium