Protective Effects of Tuber sinoaestivum –Derived Exosome‐Like Nanovesicles Against Cisplatin‐Induced Acute Liver Injury and Acute Kidney Injury

Cisplatin (CP) chemotherapy is severely limited by its dose-dependent hepatotoxicity and nephrotoxicity. This study investigates the protective effects of Tuber sinoaestivum-derived exosome-like nanovesicles (TELNs) against CP-induced acute liver injury (ALI) and acute kidney injury (AKI). Experiments were performed using CP-induced acute toxicity model mice. We evaluated hepatic and renal function by detecting serum alanine aminotransferase, creatinine, and urea nitrogen levels, histopathological examination, inflammatory cytokine levels, oxidative stress markers, and gut microbiota profiling. The results demonstrated that TELNs significantly attenuated CP-induced tissue damage and dysfunction. Mechanistic analysis revealed that TELNs reduced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), enhanced antioxidant capacity (elevated superoxide dismutase [SOD], catalase [CAT], GSH; decreased MDA), and restored gut microbiota diversity by modulating beneficial and harmful bacterial abundances. Furthermore, PICRUSt analysis indicated TELNs influenced metabolic pathways such as glutathione metabolism and DNA repair. In conclusion, TELNs confer remarkable protection against CP-induced ALI and AKI through multi-mechanistic actions, positioning them as a promising natural dietary supplement or adjuvant therapy to enhance the safety profile of CP-based chemotherapy.