Abstract

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. 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.

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