Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Bahia, 45029-094, Brazil.
Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Bahia, 45029-094, Brazil.
Clin Exp Nephrol. 2024 Aug;28(8):711-727. doi: 10.1007/s10157-024-02490-x. Epub 2024 Apr 27.
Cisplatin (CP) is a chemotherapy drug widely prescribed to treat various neoplasms. Although fundamental for the therapeutic action of the drug, its cytotoxic mechanisms trigger adverse effects in several tissues, such as the kidney, liver, and heart, which limit its clinical use. In this sense, studies point to an essential role of damage to nuclear and mitochondrial DNA associated with oxidative stress, inflammation, and apoptosis in the pathophysiology of tissue injuries. Due to the limitation of effective preventive and therapeutic measures against CP-induced toxicity, new strategies with potential cytoprotective effects have been studied. Therefore, this article is timely in reviewing the characteristics and main molecular mechanisms common to renal, hepatic, and cardiac toxicity previously described, in addition to addressing the main validated strategies for the current management of these adverse events in clinical practice. We also handle the main promising antioxidant substances recently presented in the literature to encourage the development of new research that consolidates their potential preventive and therapeutic effects against CP-induced cytotoxicity.
顺铂(CP)是一种广泛用于治疗各种肿瘤的化疗药物。尽管它是药物治疗作用的基础,但它的细胞毒性机制会在肾脏、肝脏和心脏等多种组织中引发不良反应,从而限制了其临床应用。在这种情况下,研究表明与氧化应激、炎症和细胞凋亡相关的核和线粒体 DNA 损伤在组织损伤的病理生理学中起着至关重要的作用。由于针对 CP 诱导的毒性的有效预防和治疗措施有限,因此已经研究了具有潜在细胞保护作用的新策略。因此,本文及时回顾了先前描述的肾、肝和心脏毒性的特征和主要分子机制,并讨论了当前临床实践中管理这些不良反应的主要验证策略。我们还处理了最近在文献中提出的主要有前途的抗氧化物质,以鼓励开展新的研究,巩固它们对 CP 诱导的细胞毒性的潜在预防和治疗作用。