[Protective mechanism of urolithin A against alcoholic kidney injury through ferroptosis regulation].

) light chain (xCT), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1). Network pharmacology was employed to identify the core ferroptosis targets of UA in protecting against kidney injury. Results Alcohol exposure significantly elevated the levels of CREA, BUN, MDA, KIM-1 and inflammatory cytokines, while decreasing GSH level. UA administration markedly alleviated these changes. In addition, UA significantly suppressed the alcohol-induced increase in iron content and the decreases in GPx4, xCT, Nrf2, and HO-1 protein levels. Seven core target molecules were identified through network pharmacology analysis. Inhibition of SIRT1, the core target, significantly antagonized the protective effects of UA on the Nrf2 pathway, ferroptosis, oxidative kidney injury, and renal function at both cellular and animal levels. Conclusion Alcohol exposure induces significant oxidative injury and impairs kidney function. UA activates the Nrf2 signaling pathway via the core target SIRT1, thereby inhibiting ferroptosis and alleviating alcohol-induced oxidative injury and kidney dysfunction.