A combination of gliclazide and metformin attenuates obesity-induced polycystic ovary syndrome in female Wistar rats

Anam Moazzam; Ammara Saleem; Shahid Shah; Liaqat Hussain; Mirza Muhammad Faran Ashraf Baig; Abdulrahman Alshammari; Norah A Albekairi; Muhammad Furqan Akhtar

doi:10.1016/j.heliyon.2024.e29015

A combination of gliclazide and metformin attenuates obesity-induced polycystic ovary syndrome in female Wistar rats

Heliyon. 2024 Apr 2;10(7):e29015. doi: 10.1016/j.heliyon.2024.e29015. eCollection 2024 Apr 15.

Authors

Anam Moazzam¹, Ammara Saleem², Shahid Shah³, Liaqat Hussain², Mirza Muhammad Faran Ashraf Baig⁴, Abdulrahman Alshammari⁵, Norah A Albekairi⁵, Muhammad Furqan Akhtar¹

Affiliations

¹ Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore Campus, Lahore, 5400, Pakistan.
² Department of Pharmacology, Government College University Faisalabad, Faisalabad, 38000, Pakistan.
³ Department of Pharmacy Practice, Government College University, Faisalabad, 38000, Pakistan.
⁴ Department of Chemistry, The Hong Kong University of Science and Technology, Hong Kong, SAR, China.
⁵ Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh, 11451, Saudi Arabia.

Abstract

Presently, it is known that the progression of obesity concomitantly leads to polycystic ovary syndrome and infertility. This study aimed to evaluate the potential effects of metformin (M; insulin secretagogues) and gliclazide (G; insulin sensitizer) alone and their combination at different doses to treat obesity-induced PCOS. High high-fat diet was given to all female Wistar rats for nine weeks to induce obesity except for the normal control group which received a normal chow diet. Estradiol valerate (0.8 mg/kg) was also given to all obese rats to induce polycystic ovarian syndrome. After the induction, M (100, 300 mg/kg) and G (5, 10 mg/kg) were given orally either individually or in combination for 28 days. The notable (p < 0.0001) reduction in body weight and blood glucose level was observed in treatment groups in contrast to disease control (DCG). The marked (p < 0.05-0.0001) decrease in hemocylated hemoglobin, serum insulin, cholesterol, triglycerides, and testosterone was observed in treated groups, notably in combination groups (M100+G10 mg/kg) in contrast to DCG. There was a considerable (p < 0.01-0.0001) increase in progesterone E2, estradiol, luteinizing, and follicle-stimulating hormones in treated groups as compared to DCG. Treatment with M and G treated groups also exhibited marked (p < 0.05-0.0001) increases in SOD, CAT, and GSH while decreased in NO and MDA levels in ovary tissue as evidenced by the histological study of the ovary. Treatment with M and G alone and in combination significantly (p < 0.0001) restored the serum IL-6, NrF2, and NF-κB levels as compared to DCG. The results inveterate that the M and G combination (M100+G10, and M300+G10) was useful in treating obesity-induced infertility due to antioxidant properties, hypolipidemic effects, and modulation of inflammatory markers.

Keywords: Follicle stimulating hormone; Gliclazide; High fat diet; IL-6; Luteinizing hormone; Metformin; NF-κB; NrF2; Obesity; Polycystic ovarian syndrome.