A Comprehensive Perspective of Cisplatin-induced Nephrotoxicity

Introduction: Cisplatin is a highly effective anticancer agent used against many solid tumors; however, the nephrotoxicity caused by this drug is a serious limitation. Cisplatin stimulates the production of reactive oxygen species (ROS), which orchestrate the release of numerous inflammatory cytokines. This cytokine-rich microenvironment promotes apoptosis and necrosis, ultimately leading to drug-induced nephrotoxicity. The increased formation of free radicals, such as hydrogen peroxide, superoxide anion, and hydroxyl radical, along with the decreased activity of antioxidant enzymes like superoxide dismutase, catalase, and glutathione peroxidase, further intensifies nephrotoxicity, largely due to reduced glutathione (GSH) levels in kidney cells. Methods: Data were collected from scientific databases, including PubMed, ScienceDirect, and Google Scholar. The information necessary for a detailed explanation of the mechanisms underlying cisplatin-induced nephrotoxicity was gathered, reviewed, and analyzed. Results: Cisplatin-induced nephrotoxicity leads to lipid peroxidation, protein oxidation, mitochondrial dysfunction, and DNA damage, ultimately resulting in cellular injury and kidney dysfunction. Numerous scientific studies have elucidated the mechanisms underlying cisplatininduced nephrotoxicity, particularly the involvement of signal transduction pathways that contribute to reduced GFR, inflammation, apoptosis, and tubular cell death. The extensive damage observed in the proximal convoluted tubule is largely attributed to the activation of MAPK pathways, including ERK, JNK, and p38. Conclusion: This review aims to provide a clear overview of findings from existing scientific literature on the mechanisms of cisplatin-induced nephrotoxicity. It also summarizes treatments that have shown promising results in preclinical studies, while incorporating insights from recent research on cisplatin-induced renal toxicity.