Department of Pharmaceutical Sciences, College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Biomolecules. 2022 Aug 5;12(8):1078. doi: 10.3390/biom12081078.
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.
顺铂是一种经美国食品药品监督管理局批准的抗癌药物，广泛用于治疗各种实体瘤。然而，顺铂严重的不良反应，特别是肾毒性，限制了其临床和药物应用。本综述涵盖了顺铂诱导肾毒性的主要机制，包括氧化应激、炎症和肾纤维化。特别是，我们在 NAD 依赖性氧化还原酶的背景下综述了顺铂肾损伤的潜在机制，包括线粒体复合物 I、NAD 激酶、CD38、沉默调节蛋白、多聚 ADP 核糖聚合酶和烟酰胺核苷酸转氢酶（NNT），以及它们在天然产物减轻顺铂诱导的肾损伤中的潜在作用。我们还介绍了涉及小鼠和大鼠的顺铂诱导肾损伤动物模型的一般制备程序。我们强调，需要更多的研究来剖析每个 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参与，同时深入研究 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。
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