Protective effects of GABA against metabolic and reproductive disturbances in letrozole induced polycystic ovarian syndrome in rats

J Ovarian Res. 2017 Sep 15;10(1):62. doi: 10.1186/s13048-017-0359-7.

Abstract

Background: PCOs is a heterogeneous disorder with anovulation/oligo ovulation usually taken as oligo menorrhoea or amenorrhoea, hyperandrogenemia, hirsutism, acne, androgen alopecia and polycystic ovaries as the key diagnostic feathers. The study was undertaken to investigate the possible protective and ameliorating effects of GABA in Letrozole induced PCOS model in rats by targeting insulin resistance.

Methods: PCOs in Adult female rat was induced by the daily gastric administration of letrozole (1 mg/kg/day) in CMC (0.5%) for 36 days. Rats were given metformin (2 mg/kg), GABA (100 mg/kg/day) and GABA (500 mg/kg/day) along with letrozole. One group severed as vehicle control. On the 37 day, the animals were euthanized, and anthropometrical, biochemical (glucose, insulin, lipids, testosterone, Estradiol, Progesterone, oral glucose tolerance test, total protein content in ovary, cholesterol level, triglyceride, HDL, LDL), Antioxidants (CAT, POD, GSR, ROS, GSH, TBARS), and histopathological evaluation of ovaries were carried out. Daily colpocytological examination was also carried out until the termination.

Results: Both the doses of GABA significantly reduced body weight, body mass index and testosterone. While the levels of CAT, SOD, POD and Estradiol (E2) were significantly increased in the both doses of GABA. A favourable lipid profile, normal glucose tolerance, and decreased in the percentage of estrus smears were observed. Histopathological examination of ovary revealed a decreased in the number of cystic follicles, and decreased in the adipocytes respectively. The effects observed with GABA were comparable to that with metformin.

Conclusion: The results suggest that GABA treatment has shown protective effect in PCOs and provide beneficial effect either by reducing insulin resistance or by inducing antioxidant defence mechanisms.

Keywords: Cysts; ELISA; Follicles; Gamma amino butyric acid; Oxidative stress.

MeSH terms

  • Androgen Antagonists / pharmacology
  • Androgen Antagonists / therapeutic use*
  • Animals
  • Blood Glucose / analysis
  • Body Weight / drug effects
  • Catalase / metabolism
  • Estradiol / blood
  • Female
  • Insulin Resistance
  • Letrozole
  • Nitriles
  • Ovary / drug effects
  • Ovary / metabolism
  • Ovary / pathology
  • Peroxidase / metabolism
  • Polycystic Ovary Syndrome / chemically induced
  • Polycystic Ovary Syndrome / drug therapy*
  • Polycystic Ovary Syndrome / metabolism
  • Polycystic Ovary Syndrome / pathology
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*
  • Rats
  • Reproduction / drug effects
  • Superoxide Dismutase / metabolism
  • Testosterone / blood
  • Triazoles
  • gamma-Aminobutyric Acid / pharmacology
  • gamma-Aminobutyric Acid / therapeutic use*

Substances

  • Androgen Antagonists
  • Blood Glucose
  • Nitriles
  • Protective Agents
  • Triazoles
  • Testosterone
  • Estradiol
  • gamma-Aminobutyric Acid
  • Letrozole
  • Catalase
  • Peroxidase
  • Superoxide Dismutase