Icaritin Ameliorates Cisplatin-Induced Mitochondrial Metabolic Dysfunction-Associated Nephrotoxicity and Synergistically Potentiates Its Antitumor Efficacy.

ABSTRACT: Cisplatin (CDDP) is a highly effective chemotherapy drug with broad clinical utility. Yet its therapeutic application is significantly constrained by off-target toxicities, especially nephrotoxicity. However, the molecular mechanisms underlying CDDP-induced kidney injury remain incompletely elucidated. Here, integrated multi-omics approaches are employed to dissect the pathophysiology of CDDP nephrotoxicity and uncover that CDDP directly binds to mitochondrial proteins, causing metabolic dysfunction and impairing mitochondrial respiration. Additionally, CDDP triggers mitochondrial reactive oxygen species generation, activating the nuclear factor kappa-B (NF-κB) signaling pathway and downstream inflammatory effectors. scRNA-seq analysis reveals remarkable cellular heterogeneity in the renal

SUBMITTER: Luo P 

PROVIDER: S-EPMC12866805 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature