Proanthocyanidins Attenuate Cisplatin-Induced Acute Kidney Injury and are Associated With Reshaping Gut Microbiota and Restoring Redox Homeostasis.

Cisplatin-induced acute kidney injury (AKI) is a dose-limiting chemotherapy complication laking effective clinical interventions. This study investigated the protective mechanisms of proanthocyanidins (PACs), a promising food-derived polyphenol, against cisplatin-induced systemic toxicity in C57BL/6 mice. Multi-omics integration combining 16S rRNA sequencing and renal transcriptomics, was employed to identify microbial-metabolic signaling nodes. Notably, 7-day PAC pretreatment (25 or 50 mg/kg/day) significantly alleviated renal dysfunction, normalized serum creatinine, blood urea nitrogen, reinforced renal antioxidant defenses, and suppressed kidney inflammation. Transcriptomic profiling revealed that cisplatin-induced renal damage was associated with the dysregulation of the cAMP signaling pathway, which was effectively reversed by PACs. Furthermore, 16S rRNA sequencing revealed that PACs restructured the gut microbiota by suppressing the pathogenic taxa (Alistipes and CAG_485) and enriching beneficial taxa (Muribaculaceae). Integrated network analysis further linked these microbial shifts to the stabilization of renal cAMP signaling and redox homeostasis, suggesting a coordinated gut-kidney crosstalk. In conclusion, PACs function as a multifaceted food-derived adjuvant that potentially attenuates cisplatin-induced AKI, providing a molecular framework for gut-targeted nutritional intervention in chemotherapy-induced systemic toxicity.