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Evaluation of the therapeutic effects of arbutin on cisplatin‐induced ovarian toxicity in rats through endoplasmic reticulum stress and Nrf2 pathway
Reproductive Biology ( IF 2.1 ) Pub Date : 2023-11-16 , DOI: 10.1016/j.repbio.2023.100824
Elif Ayazoglu Demir 1 , Ahmet Mentese 2 , Zeynep Sagnak Yilmaz 3 , Nihal Turkmen Alemdar 4 , Selim Demir 5 , Yuksel Aliyazicioglu 2
Affiliation  

Arbutin (ARB) is a glycosylated hydroquinone with potent antioxidant effects. Although cisplatin (CP) is widely used in chemotherapy, its toxicity in healthy tissues, including ovotoxicity, is an insurmountable problem. This study aimed to evaluate the therapeutic effect of ARB against CP-related ovototoxicity by including nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in rats for the first time. Rats treated one dose of CP (5 mg/kg) on the first day, followed by ARB (5 and 10 mg/kg) for three days. Serum reproductive hormone levels were determined using ELISA kits. Oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers in ovarian tissue were also determined colorimetrically. In addition, how CP affects Nrf2 pathway and the effect of ARB on this situation were also addressed. ARB treatment reduced the levels of markers of OS, inflammation, ERS and apoptosis in ovarian tissue of CP-stimulated animals. ARB regenerated the depleted antioxidant system by triggering Nrf2 pathway in the ovarian tissues of animals stimulated by CP. Histological findings also supported the therapeutic efficacy of ARB. The results indicate that ARB may have therapeutic effects against CP-induced reproductive toxicity with its Nrf2 activator potential. ARB should be tested in more extensive studies as a new generation chemopreventive candidate molecule.



中文翻译:

通过内质网应激和Nrf2通路评价熊果苷对顺铂所致大鼠卵巢毒性的治疗作用

熊果苷 (ARB) 是一种糖基化氢醌,具有有效的抗氧化作用。尽管顺铂(CP)广泛用于化疗,但其对健康组织的毒性,包括卵毒性,是一个难以克服的问题。本研究旨在首次通过在大鼠中纳入核因子红细胞2相关因子2(Nrf2)通路来评估ARB对CP相关卵毒性的治疗效果。大鼠在第一天接受一剂 CP(5 毫克/千克)治疗,随后接受三天 ARB(5 和 10 毫克/千克)治疗。使用 ELISA 试剂盒测定血清生殖激素水平。还通过比色法测定卵巢组织中的氧化应激(OS)、炎症、内质网应激(ERS)和细胞凋亡标记物。此外,还讨论了CP如何影响Nrf2通路以及ARB对此情况的影响。ARB 治疗降低了 CP 刺激动物卵巢组织中 OS、炎症、ERS 和细胞凋亡标志物的水平。ARB 通过触发 CP 刺激的动物卵巢组织中的 Nrf2 通路来再生耗尽的抗氧化系统。组织学结果也支持了 ARB 的治疗效果。结果表明,ARB 可能因其 Nrf2 激活剂潜力而对 CP 诱导的生殖毒性具有治疗作用。ARB 应该作为新一代化学预防候选分子进行更广泛的研究测试。

更新日期:2023-11-17
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