Background. Cisplatin (cis-diaminedichloroplatinum, CDDP) is a broad-spectrum antineoplastic agent. However, CDDP has been blamed for its nephrotoxicity, which is the main dose-limiting adverse effect. Ganoderma lucidum (GL), a medicinal mushroom, has antioxidant and inflammatory activities. Therefore, this study is aimed at finding out the potential nephroprotection of GL against CDDP-induced nephrotoxicity in rats and the possible molecular mechanisms including the EGFR downstream signaling, apoptosis, and autophagy. Methods. Rats were given GL (500 mg/kg) for 10 days and a single injection of CDDP (12 mg/kg, i.p). Results. Nephrotoxicity was evidenced by a significant increase in renal indices and oxidative stress markers. Additionally, CDDP showed a plethora of inflammatory and apoptotic responses as evidenced by a profound increase of HMGB-1, NF-κB, and caspase-3 expressions, whereas administration of GL significantly improved all these indices as well as the histopathological insults. Renal expression of EGFR showed a similar trend after GL administration. Furthermore, activation of autophagy protein, LC3 II, was found to be involved in GL-mediated nephroprotection correlated with the downregulation of apoptotic signaling, caspase-3 and terminal deoxynucleotidyl transferase (TDT) renal expressions. Conclusion. These results suggest that GL might have improved CDDP-induced nephrotoxicity through antioxidant, anti-inflammatory, and autophagy-mediated apoptosis mechanisms and that inhibition of EGFR signaling might be involved in nephroprotection.

中文翻译：

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灵芝通过抑制表皮生长因子受体信号传导和自噬介导的细胞凋亡来预防顺铂诱导的肾毒性。

背景。顺铂（cis-diaminedichloroplatinum，CDDP）是一种广谱抗肿瘤剂。然而，CDDP 因其肾毒性而受到指责，这是主要的剂量限制性副作用。灵芝 (GL) 是一种药用蘑菇，具有抗氧化和抗炎活性。因此，本研究旨在探索 GL 对 CDDP 诱导的大鼠肾毒性的潜在肾保护作用以及可能的分子机制，包括 EGFR 下游信号传导、细胞凋亡和自噬。方法。大鼠给予 GL (500 mg/kg) 10 天并单次注射 CDDP (12 mg/kg, ip)。结果. 肾脏指数和氧化应激标志物的显着增加证明了肾毒性。此外，CDDP 表现出过多的炎症和细胞凋亡反应，HMGB-1、NF- κ B 和 caspase-3 表达的显着增加就是证明，而 GL 的施用显着改善了所有这些指标以及组织病理学损伤。给予 GL 后 EGFR 的肾表达显示出类似的趋势。此外，发现自噬蛋白 LC3 II 的激活与 GL 介导的肾保护有关，与凋亡信号、caspase-3 和末端脱氧核苷酸转移酶 (TDT) 肾脏表达的下调相关。结论. 这些结果表明，GL 可能通过抗氧化、抗炎和自噬介导的细胞凋亡机制改善 CDDP 诱导的肾毒性，并且 EGFR 信号传导的抑制可能参与肾保护。