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Docosahexaenoic acid attenuates cisplatin nephrotoxicity by restoring mitophagy

Year: 2026

Type: article

Abstract: Cisplatin exhibits potent antitumor efficacy but also causes dose-dependent nephrotoxicity mediated through apoptosis of renal tubular epithelial cells, which limits its clinical application. Cisplatin induces significant mitophagy in these cells; however, the mechanisms underlying its effects on apoptotic processes remain incompletely elucidated. This study investigated the mechanism by which the polyunsaturated fatty acid docosahexaenoic acid (DHA) modulates mitophagy to alleviate cisplatin nephrotoxicity. A cisplatin-induced (15 mg/kg, intraperitoneal) acute kidney injury model was established in C57BL/6J mice, with the intervention group receiving albumin-conjugated DHA (4 mg/kg). Systematic analyses revealed that cisplatin perturbed lysosomal degradation, which led to accumulation of dysfunctional mitochondria and increased apoptosis due to impaired mitophagic flux. DHA ameliorated lysosomal dysfunction, enhanced clearance of dysfunctional mitochondria, and suppressed apoptosis. Our findings suggest that blockade of mitophagic flux is a pivotal mechanism underlying cisplatin nephrotoxicity and that DHA-mediated restoration of mitophagy is a promising therapeutic strategy.

Source: Scientific Reports

DOI: 10.1038/s41598-026-62168-0

Authors: Yuxian Zhuang, Zhenying Zuo, Chen Yang, Shangmei Li, Huafeng Liu, Kaipeng Jing

Institution: Guangdong Medical College

Language: English

Topic: Chemotherapy-induced organ toxicity mitigation

Subfield: Pathology and Forensic Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,690