Cisplatin, one of the most common antitumor agents, is widely applied to treat various cancerous diseases and is included in the World Health Organization Model List of Essential Medicines. Cisplatin therapy is used to treat 10–20% of all cancerous cases, and its cure rate is especially high in testicular cancer (over 90%). However, a major side effect of this anticancer drug is nephrotoxicity, limiting treatment effect and reducing the quality of life in cancer patients. Muscone, an odoriferous constituent of musk, was confirmed to inhibit cisplatin-induced LLC-PK1 kidney proximal tubule cell death in a dose-dependent manner. In term of renal protective mechanism, muscone inhibited cisplatin oxidative toxicity by decreasing reactive oxygen species (ROS) level and stimulating HO-1 expression. Muscone also exerted anti-inflammation effect through inhibition of p38 phosphorylation. Furthermore, muscone mitigated cisplatin-induced apoptosis in LLC-PK1 cells via both intrinsic and extrinsic pathways by inhibiting pro-apoptotic protein Bax expression, and cleaved caspase-3, 7, and 8; and increase of anti-apoptotic protein Bcl-2 level. In addition, the anti-apoptotic effect of muscone also was enhanced by preventing p53 expression and its phosphorylation. Our study showed that muscone may be a potential protective agent against cisplatin-induced nephrotoxicity.

中文翻译：

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Muscone 对 LLC-PK1 细胞顺铂肾毒性的预防作用

顺铂是最常见的抗肿瘤药物之一，广泛应用于治疗多种癌症疾病，并被列入世界卫生组织基本药物标准清单。顺铂疗法用于治疗所有癌症病例的 10-20%，其治愈率在睾丸癌中尤其高（超过 90%）。然而，这种抗癌药物的一个主要副作用是肾毒性，限制了治疗效果并降低了癌症患者的生活质量。Muscone 是麝香的一种有气味的成分，被证实能够以剂量依赖性方式抑制顺铂诱导的 LLC-PK1 肾近曲小管细胞死亡。在肾脏保护机制方面，麝香酮通过降低活性氧（ROS）水平和刺激HO-1表达来抑制顺铂的氧化毒性。Muscone 还通过抑制 p38 磷酸化发挥抗炎作用。此外，muscone 通过抑制促凋亡蛋白 Bax 表达和裂解 caspase-3、7 和 8，通过内在和外在途径减轻顺铂诱导的 LLC-PK1 细胞凋亡。并增加抗凋亡蛋白Bcl-2水平。此外，muscone的抗凋亡作用还通过阻止p53表达及其磷酸化而增强。我们的研究表明，麝香酮可能是对抗顺铂引起的肾毒性的潜在保护剂。