Cisplatin-induced renal injury: ROS-mediated oxidative stress — mechanism and antioxidant intervention strategies

Cisplatin, a widely utilised anti-cancer agent, is severely limited in clinical practice due to its various associated toxicities, among which nephrotoxicity is particularly prominent. Cisplatin-induced acute kidney injury is mainly characterized by proximal renal tubular epithelial cell injury, involving many complex molecular mechanisms. Recent numerous studies have identified oxidative stress as a core of cisplatin-induced nephrotoxicity, which affects the generation of reactive oxygen species ( ROS ) and the disruption of the antioxidant defense system. ROS not only directly damages biological macromolecules but also activates multiple downstream signaling pathways, including cellular apoptosis, DNA damage, inflammation, endoplasmic reticulum stress, and autophagy, which jointly promote the progression of kidney injury. Currently, a variety of drugs have demonstrated renal protection by enhancing antioxidant capacity in preclinical studies. However, their clinical translation still faces challenges. This review systematically summarizes the molecular sources of oxidative stress, the downstream signal cascade reactions, and the therapeutic applications of various antioxidant drugs in cisplatin-induced nephrotoxicity, with the aim of providing theoretical basis for the development of drugs to alleviate the nephrotoxicity caused by cisplatin.