顺铂（CIS）是一种广泛用于治疗多种癌症的化疗药物。它对细胞产生有害影响，限制了其作为抗肿瘤药物的临床应用，如睾丸损伤。吡格列酮（PIO）是一种过氧化物酶体增殖剂活化受体γ（PPAR-γ）激动剂，用于治疗2型糖尿病。研究报告显示PIO在不同组织中具有抗炎和抗氧化作用。本研究旨在探讨PIO在顺铂诱导的睾丸毒性大鼠模型中的作用，并探讨Toll样受体（TLR4）/髓样分化因子88（MyD88）/核因子-kappa B（NF-kB）信号通路的可能作用。大鼠在第一天接受一剂顺铂（7mg/kg, IP）和连续7天的PIO（10mg/kg, P.O.）治疗。治疗结束后，大鼠被处死。测定睾丸重量、组织病理学改变和血清睾酮水平。此外，收集组织样本以估计氧化应激参数、炎症标志物和TLR4/MyD88/NF-kB信号的确定PIO与CIS同时治疗显著改善了睾丸重量、组织病理学改变和血清睾酮水平的变化。此外，PIO同时治疗消除了CIS治疗引起的氧化应激状态和炎症标志物。此外，PIO抑制了CIS治疗激活的TLR4、MyD88和NF-κBp65表达水平。这些发现表明，PIO通过抑制TLR4/MyD88/NF-kB信号通路可以保护大鼠免受顺铂诱导的睾丸毒性的影响。版权所有 © 2023. 由 Elsevier GmbH 发布。

Cisplatin (CIS) is a chemotherapeutic agent widely used to cure several cancers. It exerts detrimental cellular effects that restrain its clinical application as an antineoplastic agent, as testicular damage. Pioglitazone (PIO), a peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist, is used to treat type-2 diabetes mellitus. PIO has been reported to exert anti-inflammatory and antioxidant effects in different tissues. The present study aimed to investigate the effect of PIO in a rat model of cisplatin-induced testicular toxicity and address the possible role of the Toll-like receptors (TLR4) / myeloid differentiation factor 88 (MyD88) / nuclear factor-kappa B (NF-kB) signal pathway.Rats received a single dose of cisplatin (7 mg/kg, IP) on the first day and PIO (10 mg/kg, P.O.) for 7 days. At the end of the treatment period, rats were killed. Testicular weights, histopathological alterations, and serum testosterone levels were determined. Moreover, tissue samples were collected for the estimation of oxidative stress parameters, inflammatory markers, and the determination of TLR4 /MyD88/NF-kB signaling.Concurrent PIO administration with CIS markedly improved testicular weights, histopathological alteration, and serum testosterone level changes. Moreover, Concurrent PIO administration abrogated oxidative stress status and inflammatory markers caused by CIS administration. Furthermore, PIO inhibited the expression levels of TLR4, MyD88, and NF-κBp65, proteins that are activated by CIS administration.These findings suggested that PIO can protect against cisplatin-induced testicular toxicity in rats through inhibition of the TLR4 /MyD88/NF-kB signal pathway.Copyright © 2023. Published by Elsevier GmbH.