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

## TL;DR

GV1001, a peptide, protects the kidneys from cisplatin damage by maintaining mitochondrial health and reducing inflammation and cell death.

## Contribution

GV1001 is shown to directly target mitochondrial mechanisms to prevent cisplatin-induced nephrotoxicity.

## Key findings

- GV1001 reduces cisplatin-induced kidney damage in mice by reversing histopathological and inflammatory changes.
- The peptide preserves mitochondrial function by maintaining membrane potential and ATP production in renal cells.
- GV1001 suppresses apoptosis and ROS levels, protecting against cisplatin toxicity in kidney epithelial cells.

## Abstract

What are the main findings?
GV1001 prevents cisplatin-induced nephrotoxicity in mice, as evidenced by the reversal of cisplatin-induced histopathological abnormalities, inflammatory responses, apoptotic cell death, and elevations in serum and renal injury markers.GV1001 preserves mitochondrial integrity and function against cisplatin-induced damages.

GV1001 prevents cisplatin-induced nephrotoxicity in mice, as evidenced by the reversal of cisplatin-induced histopathological abnormalities, inflammatory responses, apoptotic cell death, and elevations in serum and renal injury markers.

GV1001 preserves mitochondrial integrity and function against cisplatin-induced damages.

What is the implication of the main finding?
GV1001 can serve as a novel protective agent against cisplatin-induced nephrotoxicity.

GV1001 can serve as a novel protective agent against cisplatin-induced nephrotoxicity.

GV1001, a multifunctional peptide, has shown numerous biomedical activities, including antioxidant, anti-inflammatory, anti-Alzheimer’s, and anti-atherosclerotic effects, and protects mitochondria from cytotoxic agents. Cisplatin is a widely used chemotherapeutic agent against cancers, but its clinical utility is limited by nephrotoxicity driven by mitochondrial dysfunction in renal epithelial cells. Here, we investigated whether GV1001 protected against cisplatin-induced nephrotoxicity (CIN) in vivo and preserved mitochondrial integrity in human renal epithelial cells in vitro. In mice, GV1001 substantially mitigated CIN by significantly reducing histological damage, kidney injury marker expression, macrophage infiltration, endothelial-to-mesenchymal transition, inflammation, and apoptosis. In cultured renal epithelial cells, GV1001 maintained mitochondrial membrane potential, preserved ATP production, and prevented mitochondrial membrane peroxidation possibly by binding to cardiolipin. GV1001 also reduced the level of reactive oxygen species (ROS), suppressed cytochrome c release into the cytosol, and inhibited activation of apoptosis-related pathways elicited by cisplatin. Collectively, these findings demonstrated that GV1001 might protect kidney from cisplatin through maintaining mitochondrial structure and function and suppressing downstream injury cascades in renal epithelial cells. By directly targeting the mitochondrial mechanisms underlying cisplatin toxicity, GV1001 represents as a promising therapeutic strategy to mitigate CIN and improve the safety of cisplatin-based chemotherapy.