Exenatide improves cisplatin induced ovarian damage through NLRP3, Nrf-2, and TLR4 pathways.

Gül O Doğan, Oytun Erbaş
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Abstract

Objective: Cisplatin (CP) toxicity causes ovarian damage by oxidative stress, inflammation and fibrosis. The aim of the present study is to investigate the possible beneficial effects of exenatide on the experimental ovarian damage model produced by CP.

Method: For 14 rats, CP was administered by intraperitoneally (i.p) twice a week for 5 weeks. No drug was administered to the remainder of rats (n = 7) (Group 0). The rats taken CP were divided into two groups. Group 1 rats (n = 7) were given 1 mL/kg/day saline i.p., and Group 2 rats (n = 7) was given with 20 μg/kg/day exenatide.

Results: The number of primordial, primary, secondary, and tertiary follicle was significantly lower in Group1 compared with Group 0 and Group 2. The ovarian fibrosis percent was significantly higher in Group 1 than Group 0 and 2. The plasma anti-Mullerian hormone value was lower in Group1compared with Group 0 and 2. Over Nuclear factor-erythroid factor 2-related factor 2 level, Over Toll-like receptor 4 level and over nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor 3 were higher in Group 1 compared with Group 0 and 2.

Conclusion: Exenatide has possible beneficial effect on ovarian damage induced by CP by anti-inflammatory actions and can be a promising candidate for ovarian damage caused by CP.

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艾塞那肽通过NLRP3、Nrf-2和TLR4途径改善顺铂诱导的卵巢损伤。
目的:顺铂(CP)毒性通过氧化应激、炎症和纤维化导致卵巢损伤。本研究旨在探讨艾塞那肽对顺铂造成的实验性卵巢损伤模型可能产生的有益影响:方法:对14只大鼠腹腔注射CP,每周两次,连续5周。其余大鼠(n = 7)不给药(0 组)。服用氯化石蜡的大鼠分为两组。第 1 组大鼠(n = 7)每天注射 1 mL/kg 生理盐水,第 2 组大鼠(n = 7)每天注射 20 μg/kg 艾塞那肽:结果:与0组和2组相比,1组大鼠的原始卵泡、初级卵泡、二级卵泡和三级卵泡数量均显著减少;1组大鼠的卵巢纤维化率显著高于0组和2组。与 0 组和 2 组相比,1 组的血浆抗苗勒氏管激素值较低。结论:与0组和2组相比,1组的核因子-红细胞因子2相关因子2水平、Toll样受体4水平和核苷酸结合域富含亮氨酸重复和含吡啶结构域的受体3水平更高:艾塞那肽可通过抗炎作用对 CP 引起的卵巢损伤产生有益影响,有望成为治疗 CP 引起的卵巢损伤的候选药物。
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