What is the clinical evidence from this study?

Study design: Other. Population: Cisplatin-induced acute kidney injury. Intervention: Albumin-conjugated docosahexaenoic acid (DHA) vs. Cisplatin alone. Primary outcome: Lysosomal dysfunction, clearance of dysfunctional mitochondria, and apoptosis.

What question did this study set out to answer?

To explore how docosahexaenoic acid (DHA) affects mitophagy to mitigate cisplatin-induced nephrotoxicity in renal tubular cells.

July 18, 2026Scientific Reports0 citationsOpen Access

Docosahexaenoic acid attenuates cisplatin nephrotoxicity by restoring mitophagy

YZYuxian Zhuang ZZZhenying Zuo CYChen Yang

Key Result

Albumin-conjugated DHA ameliorated lysosomal dysfunction, enhanced clearance of dysfunctional mitochondria, and suppressed apoptosis in a mouse model of cisplatin-induced acute kidney injury.

Key Points

To explore how docosahexaenoic acid (DHA) affects mitophagy to mitigate cisplatin-induced nephrotoxicity in renal tubular cells.
Established a cisplatin-induced acute kidney injury model in C57BL/6J mice with a dose of 15 mg/kg, administered intraperitoneally.
Intervention group received albumin-conjugated DHA at a dose of 4 mg/kg.
Conducted systematic analyses to assess lysosomal function, mitochondrial clearance, and apoptosis levels.
Cisplatin treatment caused increased apoptosis and disrupted lysosomal degradation in renal tubular cells.
DHA treatment improved lysosomal function and facilitated the clearance of dysfunctional mitochondria, reducing apoptosis.
Restoration of mitophagic flux by DHA suggests a new therapeutic strategy for preventing cisplatin nephrotoxicity.

Structured PICO

Does docosahexaenoic acid attenuate cisplatin nephrotoxicity in a mouse model of acute kidney injury?

Population

C57BL/6J mice with cisplatin-induced acute kidney injury treated with albumin-conjugated DHA.

Intervention

Albumin-conjugated docosahexaenoic acid (DHA) 4 mg/kg

Comparator

Cisplatin-induced acute kidney injury model without DHA intervention

Outcome

Mitigation of cisplatin nephrotoxicity (amelioration of lysosomal dysfunction, enhanced clearance of dysfunctional mitochondria, and suppressed apoptosis)surrogate

Docosahexaenoic acid attenuates cisplatin-induced nephrotoxicity in mice by restoring mitophagic flux and reducing apoptosis.

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.

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