Taxifolin Attenuates Cisplatin-Induced Acute Kidney Injury by Promoting Fatty Acid Oxidation.

Cisplatin-induced nephrotoxicity frequently manifests as acute kidney injury (AKI), creating a major limitation for its widespread clinical application. Taxifolin, a phytochemical flavonoid, possesses potent free radical-scavenging activity and the ability to modulate inflammatory responses. Our study focused on assessing the renoprotective capacity of taxifolin in the context of cisplatin-induced kidney damage. Cell culture studies showed that taxifolin reduced damage to human tubular epithelial cells caused by cisplatin. Furthermore, we evaluated the protective effect of taxifolin on mice with cisplatin-induced nephrotoxicity. Oral administration of taxifolin effectively mitigated both functional impairment and structural injury in renal tubules, both when administered 2 days before and 2 h following cisplatin injection. Transcriptomic analysis of renal tissues via RNA-seq revealed that taxifolin's nephroprotective effects against cisplatin toxicity may involve Fabp4-regulated lipid metabolism pathways. In both cisplatin-induced AKI mouse models and renal tubular cells, taxifolin enhanced lipid metabolism, restored cellular energy (ATP) production, and upregulated PGC-1α/PPARα expression by reversing Fabp4-impaired suppression of fatty acid beta-oxidation. Collectively, these results indicate that taxifolin exerts nephroprotective effects against cisplatin-induced AKI by modulating Fabp4-dependent fatty acid oxidation pathways, positioning it as a potential therapeutic candidate for cisplatin-associated nephrotoxicity.