Pharmacological Evaluation of Combination Effect of Ketoconazole and Metformin with N-Acetylcysteine in Letrozole Induced PCOS in Female Wistar Rats

Abstract

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder with hyperandrogenism, insulin resistance and chronic anovulation as its primary characteristics that affects a significant number of females in their reproductive age. The letrozole induced animal study on female Wistar rats makes it easier to study the pathophysiology and therapeutic effects on PCOS similar to that on humans that makes it a suitable experimental method for the evaluation of pharmacological effects of different drugs. This animal study evaluates the efficacy of ketoconazole, metformin and N-acetylcysteine (NAC) in combination and also compare its effect with respect to the individual drugs against PCOS, to reverse the hormonal and metabolic effects that were induced in the rats by letrozole.

Ketoconazole, primarily used for its antifungal effect also shows anti-androgenic properties. It inhibits the steroidogenic enzymes, that results in reducing the synthesis of androgens. Metformin helps to manage insulin sensitivity which is now commonly being used in PCOS patients. It improves ovulatory function along with reducing insulin resistance to lower the blood glucose level in females having polycystic ovary. NAC is a precursor of glutathione that acts as an antioxidant to manage oxidative stress and also provide cytoprotective effect. The combined therapy has shown a significant improvement in PCOS by suppressing the level of testosterone, luteinizing hormone and blood glucose level. Histopathological examination of ovaries of different groups have also shown the reduction in cystic follicles along with restoration of healthy corpus luteum. Thus, this study provides a potential treatment option for PCOS using the synergistic effect of ketoconazole, metformin and NAC.