Indolepropionic acid protects against renal fibrosis due to unilateral ureteral obstruction by enhancing the Nrf2 signaling pathway

Objective This study investigates the protective effect of indolepropionic acid (IPA) on renal fibrosis caused by unilateral ureteral obstruction (UUO), with a focus on the Nrf2 signaling pathway. Methods A UUO model was established in 30 male SD rats (6 weeks old) via unilateral ureteral ligation. Rats were divided into sham, model, L-IPA, M-IPA, and H-IPA groups. Pathological changes and protein expressions in renal tissues were analyzed. In vitro, HK-2 cells were cultured and subjected to hypoxia for 24 h. Cells were divided into control, model, model + IPA, and model + IPA + ML385 (Nrf2 inhibitor) groups. Fibrosis and Nrf2-related protein expressions were assessed. Results In vivo, the model group exhibited severe renal damage, accompanied by increased oxidative stress and inflammatory response. The expression of α-SMA, FN, Snail1, Smad3, TGF-β1, Keap1, and HIF-1α was elevated, while Nrf2 and HO-1 levels were decreased, all of which were reversed by IPA treatment. In vitro, IPA reversed the changes in fibrosis-related proteins, while this protective effect was blocked by ML385. Conclusion IPA ameliorates renal fibrosis by activating the Nrf2 pathway, offering a potential therapeutic strategy for renal injury.