Nipecotic Acid Ameliorates Letrozole Induced Poly Cystic Ovarian Syndrome in Female Virgin Wistar Rats by Modulating Hypothalamic-Pituitary-Gonadal (HPG) Axis Regulated by GABA.

Abstract

PCOS is a common endocrine disorder in women particularly in their reproductive age. GABA has been implicated in the pathogenesis of PCOS through its central role in the hypothalamus. Hence, in this study we investigated the effect of Nipecotic acid (NPA) in Letrozole induced PCOS in female Wistar rats as NPA has been proven as a GABA uptake inhibitor. In this study 30 female Wistar rats were divided into 5 groups each group containing 6 animals and treated as follows-Healthy control: Vehicle, 0.5% carboxymethylcellulose (CMC); Diseased control: Letrozole 1 mg/kg orally in 0.5% CMC; Test group-1: Letrozole + NPA (2.5 mg/kg i.p.); Test group-2: Letrozole + NPA (5 mg/kg i.p.) and Standard group: Letrozole + Clomiphene citrate (1 mg/kg in 0.5% CMC orally). Body weight, feed intake, water intake and vaginal smear was recorded on daily basis till the completion of the treatment tenure, whereas serum oestrogen, testosterone and GABA; ovary and uterus histopathology; lipid profile; OGTT; GsH, MDA and TNF-alpha in ovary tissue were estimated in the end of the treatment tenure. NPA treated groups demonstrated an improvement in the irregularities of the oestrous cycle with respect to PCOS control group. Further, NPA at both doses significantly (p < 0.001) reduced oxidative stress and inflammation in the ovary. It significantly (p < 0.001) reduced the serum testosterone and significantly (p < 0.001) elevated the serum oestrogen level. Histopathological reports depicted NPA reduced follicular cysts and promoted ovulation. These results emphasize the possibility of NPA as a treatment option for PCOS related reproductive and metabolic disorders, addressing the unmet need for effective PCOS management.