GV1001, an hTERT-Derived Peptide, Prevents Cisplatin-Induced Nephrotoxicity by Preserving Mitochondrial Function

GV1001, an anticancer vaccine, exhibits diverse biological activities, including antioxidant, anti-inflammatory, anti-Alzheimer’s, and anti-atherosclerotic effects, and protects mitochondria from drug-induced injury. Cisplatin, a widely used chemotherapeutic, is effective but limited by nephrotoxicity driven by mitochondrial dysfunction in renal epithelial cells. We investigated whether GV1001 could counteract cisplatin-induced kidney injury in mice and preserve mitochondrial integrity in human renal epithelial cells. In vivo, GV1001 completely mitigated cisplatin-induced nephrotoxicity. It prevented cisplatin-induced histopathological damage, kidney injury marker expression, macrophage infiltration, endothelial-to-mesenchymal transition, inflammation, and apoptosis. In vitro, GV1001 maintained mitochondrial membrane potential, preserved ATP production, and prevented mitochondrial membrane peroxidation, possibly by binding to cardiolipin. It also reduced reactive oxygen species (ROS), cytochrome c release into the cytosol, and subsequent activation of apoptosis-related pathways elicited by cisplatin. Collectively, these findings demonstrate that GV1001 protects against cisplatin-induced nephrotoxicity (CIN) by preserving mitochondrial structure and function while suppressing downstream pathological events. By directly targeting the central mechanism of cisplatin toxicity, GV1001 emerges as a promising therapeutic strategy to mitigate CIN and improve the safety of chemotherapy.