Resveratrol inhibits renal ischemia and reperfusion injury in diabetes via reducing oxidative stress, inflammation, and apoptosis.

[OBJECTIVES] The diabetic kidney is susceptible to renal ischemia/reperfusion (I/R) injury, which is associated with enhanced oxidative stress, inflammatory responses, and cell apoptosis. Resveratrol (RSV) plays a crucial role in protecting various organs against ischemia/reperfusion damage by exerting antioxidant, anti-inflammatory, and anti-apoptotic effects. However, the molecular mechanism of RSV protection against renal I/R injury in diabetic conditions remains unclear. The aim of the present study was to examine whether RSV attenuates renal I/R injury in diabetes and further clarify the underlying mechanisms.

[METHODS] Streptozotocin-induced diabetic rats and high glucose-cultured HK-2 cells were, respectively, treated with RSV before renal ischemia and hypoxia/reoxygenation induction. , cell viability, intracellular reactive oxygen species levels, and apoptosis were measured. , renal function, histology, oxidative stress level, inflammatory cytokines, and apoptosis were determined. Furthermore, the expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3, nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), toll-like receptor 4 (TLR4), and nuclear factor-κB (NF-κB) were detected.

[RESULTS] RSV improved renal function, reduced oxidative stress, inhibited inflammatory responses, and decreased apoptosis after renal ischemia/reperfusion in diabetes, accompanied by increased expression of Nrf2 and HO-1, and decreased expression of TLR4 and NF-κB. The beneficial effects of RSV were abolished by selective inhibition of Nrf2 with ML385.

[CONCLUSION] These findings indicate that RSV could attenuate renal I/R injury in diabetes, possibly by enhancing Nrf2/HO-1 signaling and suppressing the TLR4/NF-κB pathway.