GV1001 peptide shields kidneys from cisplatin damage by protecting mitochondria

Cisplatin treats many solid tumors, but its use is limited by kidney toxicity. The drug accumulates in proximal tubule cells, which have a high energy demand and many mitochondria. There it triggers oxidative stress, DNA damage and cell death. Hydration, the standard precaution, gives only partial protection, so new approaches are needed.

This study tested GV1001, a 16-amino-acid peptide derived from human telomerase reverse transcriptase that has shown antioxidant, anti-inflammatory and mitochondria-protective effects in earlier work. Thirty-two male C57BL/6J mice were split into four groups of eight: PBS control, GV1001 alone (2 mg/kg, three times weekly), cisplatin plus PBS (2.5 mg/kg, twice weekly), and cisplatin plus GV1001, all for six weeks. The team assessed kidney histology, serum markers, gene and protein expression, and apoptosis. In parallel, human kidney epithelial cells (HK-2 and normal primary cells) were exposed to cisplatin (25 μM) with or without GV1001 (10 μg/mL) to probe mitochondrial function.

In mice, cisplatin caused tubular dilation, protein casts, macrophage infiltration, and higher serum creatinine, BUN and uric acid. GV1001 co-treatment significantly reduced all of these. It also lowered the injury markers KIM-1 and NGAL, preserved E-cadherin while limiting α-SMA (an epithelial-to-mesenchymal transition shift), and suppressed TNF-α, IL-1β, IL-6 and TGF-β in kidney tissue and serum. Cisplatin-induced apoptosis fell with GV1001. GV1001 also restored expression of the OCT2 transporter and reduced cisplatin–DNA adducts, though the transporter and adduct findings are descriptive.

In cells, cisplatin reduced mitochondrial mass, depolarized the membrane, cut ATP, raised mitochondrial and cytosolic ROS, increased mitochondrial iron and lipid peroxidation, and lowered electron transport chain complexes I–IV. GV1001 reversed these effects. It blocked cytochrome c release, caspase-3 and PARP cleavage, and activation of γ-H2AX, p53, p38 and Bax. Binding assays suggested GV1001 interacts with cardiolipin, a key inner-mitochondrial-membrane lipid, in a dose-dependent way, which may explain its mitochondrial protection.

The results point to GV1001 as a candidate for protecting kidneys during cisplatin chemotherapy. Important caveats remain. Only male mice and a small sample were used, the cardiolipin binding was shown in vitro only, and the mechanism is not proven causal. The study did not test whether GV1001 leaves cisplatin's anticancer efficacy intact, which is essential for any clinical use. Human trials would be needed.