Abstract：
Cisplatin is an FDA approved anti-cancer drug that is widely used for the treatment of a variety of solid tumors. However, the severe adverse effects of cisplatin, particularly kidney toxicity, restrict its clinical and medication applications. The major mechanisms of cisplatin-induced renal toxicity involve oxidative stress, inflammation, and renal fibrosis, which are covered in this short review. In particular, we review the underlying mechanisms of cisplatin kidney injury in the context of NAD+-dependent redox enzymes including mitochondrial complex I, NAD kinase, CD38, sirtuins, poly-ADP ribosylase polymerase, and nicotinamide nucleotide transhydrogenase (NNT) and their potential contributing roles in the amelioration of cisplatin-induced kidney injury conferred by natural products derived from plants. We also cover general procedures used to create animal models of cisplatin-induced kidney injury involving mice and rats. We highlight the fact that more studies will be needed to dissect the role of each NAD+-dependent redox enzyme and its involvement in modulating cisplatin-induced kidney injury, in conjunction with intensive research in NAD+ redox biology and the protective effects of natural products against cisplatin-induced kidney injury.
摘要：
顺铂是FDA批准的抗癌药,广泛用于多种实体瘤的治疗。然而,顺铂的严重不良反应，特别是肾毒性，限制其临床和药物应用。顺铂诱导的肾毒性的主要机制涉及氧化应激，炎症,和肾脏纤维化，这些都涵盖在这篇简短的评论中。特别是,我们在NAD+依赖性氧化还原酶包括线粒体复合物I的背景下综述了顺铂肾损伤的潜在机制。NAD激酶,CD38，沉默调节蛋白，聚ADP核糖基转移酶聚合酶，和烟酰胺核苷酸转氨酶（NNT）及其在改善植物天然产物赋予的顺铂诱导的肾损伤中的潜在作用。我们还涵盖了用于创建涉及小鼠和大鼠的顺铂诱导的肾损伤的动物模型的一般程序。我们强调，需要更多的研究来剖析每种NAD+依赖性氧化还原酶的作用及其在调节顺铂诱导的肾损伤中的作用。结合NAD+氧化还原生物学和天然产物对顺铂诱导的肾损伤的保护作用的深入研究。
