Comparative Evaluation of Aldose Reductase Inhibition in Polycystic Ovarian Syndrome-Induced Rats

Polycystic ovary syndrome (PCOS) represents a spectrum of disorders, associated with hyperandrogenism, oligoanovulation, and polycystic ovaries. Aldose reductase (AR), a rate-limiting enzyme of polyol pathway, is responsible for maintenance of intracellular osmotic balance, facilitation of oocyte development, and organization of the granulosa cells in the ovary. Cyclic changes in the aldose reductase level were found during the 4-5 days estrus cycle in rat, which is regulated by gonadotropin-releasing hormone (GnRH). Irregular GnRH secretion in PCOS patients may lead to altered aldose reductase expression and ovarian dysfunction. Treatment with a novel AR inhibitor, fidarestat, has been reported to improve erythrocyte sorbitol content in diabetic patients. Hence, the potential role AR in pathogenesis of PCOS was investigated by inhibiting AR with fidarestat in PCOS-induced rats. Pre-pubertal female Sprague-Dawley rats were divided into five groups. PCOS is induced either by administering letrozole or by feeding high-fat diet for 90 days. After induction of PCOS, fidarestat treatment was given for 28 days and various parameters were measured. In PCOS-induced rats, parameters like food intake, body weight, insulin, OGTT, triglycerides, cholesterol, prolonged diestrus phase, ovary weight, and immunohistological localization AR were found to be significantly altered. Fidarestat treatment significantly improved ovary weight, ovarian aldose reductase localization in PCOS-induced rats. Improvement in all these parameters suggest involvement of aldose reductase in the pathogenesis of PCOS.