Moazzam A, et al. Heliyon, 2024, 10(7), e29015.
Recent studies have extended its therapeutic potential, exploring its combined application with metformin in the management of obesity-induced polycystic ovary syndrome (PCOS). In a study conducted on female Wistar rats, a high-fat diet was used to induce obesity and subsequent PCOS, with estradiol valerate administered to enhance the syndrome's progression. The rats were then treated with gliclazide (5, 10 mg/kg) and metformin (100, 300 mg/kg), either alone or in combination, over a period of 28 days.
The results demonstrated significant improvements across several parameters in the treated groups compared to the disease control group (DCG). Notably, a marked reduction in body weight and blood glucose levels was observed, along with decreased hemoglobin A1c, serum insulin, cholesterol, triglycerides, and testosterone. In contrast, key reproductive hormones, including progesterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), were significantly elevated in the treatment groups. Furthermore, the combination therapy of metformin and gliclazide (M100+G10 mg/kg) was particularly effective in restoring ovarian antioxidant levels, evidenced by increased superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), alongside reduced oxidative stress markers like malondialdehyde (MDA) and nitric oxide (NO).
Histological examination of ovarian tissues corroborated these biochemical findings, showing marked improvements in tissue integrity. Moreover, treatment with gliclazide and metformin significantly modulated inflammatory markers, including interleukin-6 (IL-6), Nrf2, and NF-κB, underscoring the potential of this combination therapy in addressing the multifaceted pathophysiology of obesity-induced PCOS.