Protective Role of Natural Antioxidants Against Cisplatin-Induced Nephrotoxicity in Rats

Abstract

Nephrotoxicity is the most frequent adverse effect associated with cisplatin, which limits its clinical use. One of the upstream responses that causes varying degrees of damage to the intracellular material components in a cisplatin-induced pathological response is oxidative stress. One of the first signaling molecules that goes through a number of pathogenic responses, including necrosis and apoptosis, is reactive oxygen species (ROS). According to this review, the mechanism of cisplatin-induced intracellular ROS generation is primarily caused by the consumption of endogenous antioxidants, the breakdown of antioxidant enzymes, the induction of mitochondrial crosstalk between the endoplasmic reticulum by ROS and Ca2+, and the destruction of the cytochrome P450 (CYP) system in the endoplasmic reticulum. These factors all contribute to an excessive buildup of intracellular ROS and oxidative stress. Furthermore, research showed that by lowering or even eliminating excess free radicals and also influencing other nonredox pathways, natural antioxidants may guard against cisplatin-induced nephrotoxicity. Thus, this review offers theoretical justification for the investigation and clinical use of natural antioxidants while also offering a fresh perspective on the intricate mechanism of cisplatin nephrotoxicity, potentially laying the groundwork for cisplatin's future clinical use.