Moazzam Anam, Saleem Ammara, Shah Shahid, Hussain Liaqat, Baig Mirza Muhammad Faran Ashraf, Alshammari Abdulrahman, Albekairi Norah A, Akhtar Muhammad Furqan
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore Campus, Lahore, 5400, Pakistan.
Department of Pharmacology, Government College University Faisalabad, Faisalabad, 38000, Pakistan.
Heliyon. 2024 Apr 2;10(7):e29015. doi: 10.1016/j.heliyon.2024.e29015. eCollection 2024 Apr 15.
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.
目前已知，肥胖的进展会同时导致多囊卵巢综合征和不孕症。本研究旨在评估二甲双胍（M；胰岛素促泌剂）和格列齐特（G；胰岛素增敏剂）单独使用及其不同剂量组合对治疗肥胖诱导的多囊卵巢综合征的潜在影响。除正常对照组给予正常饲料饮食外，所有雌性Wistar大鼠均给予高脂饮食9周以诱导肥胖。所有肥胖大鼠还给予戊酸雌二醇（0.8mg/kg）以诱导多囊卵巢综合征。诱导后，M（100、300mg/kg）和G（5、10mg/kg）单独或联合口服给药28天。与疾病对照组（DCG）相比，治疗组的体重和血糖水平显著降低（p<0.0001）。与DCG相比，治疗组的糖化血红蛋白、血清胰岛素、胆固醇、甘油三酯和睾酮显著降低（p<0.05 - 0.0001），尤其是联合用药组（M100 + G10mg/kg）。与DCG相比，治疗组的孕酮E2、雌二醇、促黄体生成素和促卵泡生成素显著增加（p<0.01 - 0.0001）。M和G治疗组的卵巢组织经组织学研究证实，超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽（GSH）水平显著增加（p<0.05 - 0.0001），而一氧化氮（NO）和丙二醛（MDA）水平降低。与DCG相比，单独使用M和G以及联合使用均显著（p<0.0001）恢复了血清白细胞介素-6（IL-6）、核因子E2相关因子2（NrF2）和核因子κB（NF-κB）水平。结果表明，M和G联合使用（M100 + G10和M300 + G10）由于具有抗氧化特性、降血脂作用和调节炎症标志物，对治疗肥胖诱导的不孕症有效。
