orabase and Polycystic-Ovary-Syndrome

Topics: Animals; Carboxymethylcellulose Sodium; Disease Models, Animal; Down-Regulation; Estradiol; Estrous Cycle; Female; Follicle Stimulating Hormone; Hypoglycemic Agents; Interleukin-18; Letrozole; Luteinizing Hormone; Metformin; Ovulation; Polycystic Ovary Syndrome; Rats; Testosterone; Tumor Necrosis Factor-alpha

The present study was conducted to investigate the therapeutic effects of a potent polyphenol, fisetin, on the letrozole-induced rat model of polycystic ovary syndrome (PCOS).. Twenty-four female Wistar rats (42 days old) were divided into four groups: control group (received carboxy methylcellulose (CMC 0.5 %)), PCOS group treated with letrozole (1 mg/kg), fisetin group received same dose of letrozole + fisetin (10 mg/kg), and metformin group received same dose of letrozole + metformin (300 mg/kg). At the end of the experiment, biochemical (glucose, lipid profile) and hormonal (insulin, testosterone, estradiol, and progesterone) parameters were analyzed. Histological examinations of ovaries were also conducted by hematoxylin and eosin (H&E) staining. Real-time polymerase chain reaction (PCR) and western blotting were carried out for cytochrome P450 17A1 (CYP17A1), sirtuin-1 (SIRT1), and 5' AMP-activated protein kinase (AMPK) gene expression in the ovaries. Furthermore, enzymatic activities of antioxidants including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the ovaries were analyzed by colorimetric method.. Letrozole administration resulted in a remarkable abnormality in biochemical and hormonal parameters. Fisetin normalized levels of glucose, lipid profile, homeostatic model assessment for insulin resistance (HOMA-IR), testosterone, estradiol, and progesterone. Moreover, fisetin increased expression levels of SIRT1 and AMPK, and decreased expression level of CYP17A1 in the ovaries. Additionally, fisetin showed protective effect by enhancing antioxidant activities of CAT, SOD, and GPx depleted secondary to induction of PCOS. Fisetin effects were comparable to metformin, as the standard drug used for treatment of PCOS.. Our results showed that, fisetin treatment caused significant alleviating effects by restoring PCOS-induced alterations in the key genes involved in energy homeostasis and antioxidant enzymes, suggesting that it may have a key role in combating with PCOS.

Topics: AMP-Activated Protein Kinases; Animals; Antineoplastic Agents, Phytogenic; Blood Glucose; Carboxymethylcellulose Sodium; Catalase; Disease Models, Animal; Estradiol; Female; Flavonols; Gene Expression; Glutathione Peroxidase; Humans; Insulin; Letrozole; Metformin; Ovary; Polycystic Ovary Syndrome; Progesterone; Rats; Rats, Wistar; Sirtuin 1; Steroid 17-alpha-Hydroxylase; Superoxide Dismutase; Testosterone

Insulin sensitizers like metformin and pioglitazone are clinically used since last decades for the treatment of PCOS, but their efficacy and possible role in PCOS patients remains questionable. Also, the mechanism by which these insulin sensitizers show effect is not clear.. To evaluate the effect of metformin and pioglitazone on leutinizing hormone and follicle stimulating hormone receptor mRNA expression, hyperandrogenism and insulin resistance in high fat diet induced and letrozole induced PCOS in rats.. Pre-pubertal female rats were divided into four groups: group I received normal pellet diet and group II, III and IV received high fat diet. After 105 d of dietary manipulation, metformin and pioglitazone treatment was given to group III and group IV animals respectively for 21 d. Similarly, adult female rats were divided into four groups: group I received 1% carboxymethyl cellulose (CMC) and group II, III, IV received letrozole for 21 d. After 21 d of letrozole administration, metformin and pioglitazone treatment was given to group III and group IV animals respectively for 21 d. Oral glucose tolerance test, lipid profile, fasting glucose, insulin, estrus cycle, hormonal profile, ovary weight, leutinizing hormone receptor and follicle stimulating hormone receptor mRNA expression was measured. Polycystic ovarian morphology was assessed through histopathological changes of ovary.. Metformin and pioglitazone treatment improve both metabolic and reproductive parameters of PCOS including hyperinsulinemia and hyperandrogenism. LH receptor and FSH receptor mRNA expression were altered by pioglitazone and metformin treatment.

Topics: Animals; Body Weight; Carboxymethylcellulose Sodium; Diet, High-Fat; Female; Glucose Tolerance Test; Humans; Hyperandrogenism; Hypoglycemic Agents; Insulin; Insulin Resistance; Letrozole; Metformin; Pioglitazone; Polycystic Ovary Syndrome; Rats; Rats, Sprague-Dawley; Receptors, LHRH; RNA, Messenger