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. In vitro, cell viability, intracellular Reactive Oxygen Species levels, and Apoptosis were measured. In vivo, 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.