Resveratrol ameliorates renal damage by inhibiting oxidative stress-mediated apoptosis of podocytes in diabetic nephropathy

Diabetic nephropathy (DN) is the major cause of end-stage renal disease. Resveratrol (RSV) has been shown to exert a renoprotective effect against DN, but despite research progress, the protective mechanisms of RSV have not been fully elucidated. Here, we demonstrated that RSV relieved a series of pathological characteristics of DN and attenuated oxidative stress and apoptosis in the renal tissues of diabetic (db/db) mice. In addition, RSV inhibited oxidative stress production and apoptosis in human podocytes exposed to high glucose. Furthermore, inhibition of reactive oxygen species generation by reactive oxygen species scavengers N-acetylcysteine and 2,2,6,6-tetramethyl-1-piperidinyloxy had the same anti-apoptosis effects on podocytes as did RSV. Finally, we found that 5' adenosine monophosphate-activated protein kinase (AMPK) was activated by RSV in db/db mice and podocytes exposed to high glucose. The protective effects of RSV on podocytes were suppressed by Compound C, a pharmacological inhibitor of AMPK. Together, our results indicate that RSV effectively attenuated renal damage by suppressing oxidative stress-mediated apoptosis of podocytes, which was dependent on AMPK activation. This study revealed a possible mechanism to protect podocytes against apoptosis in DN.