Resveratrol Attenuates Early Diabetic Nephropathy by Down-Regulating Glutathione S-Transferases Mu in Diabetic Rats

Diabetic nephropathy (DN) is the major cause of end-stage renal disease. Resveratrol has been shown to ameliorate hyperglycemia in diabetic rats. However, the effects of resveratrol on DN remain unknown. The aim of the present study is to investigate the effects of resveratrol on early-stage DN. Diabetes was induced by streptozotocin injection in male Wistar rats. The diabetic rats were treated with resveratrol at a dose of 20 mg/kg body weight for 8 weeks. Plasma glucose, creatinine, kidney/body weight ratio, and 24-h urinary protein were determined. The renal pathological changes were examined with periodic acid Schiff staining, and renal mesangial cells were cultured in high glucose concentrations with indicated concentrations of resveratrol (2.5, 5.0, and 10.0 mu mol/L). The proliferation of mesangial cells was evaluated by methylthiazoletetrazolium assay. Expressions of glutathione S-transferases Mu (GSTM) and nuclear factor erythroid 2-related factor 2 (Nrf2) were detected by western blot, and apoptosis was analyzed using a flow cytometer. Resveratrol reduced plasma glucose, creatinine, and urinary protein excretion, and attenuated renal hypertrophy. Moreover, resveratrol also reduced the expression of GSTM in diabetic rats. In vitro, resveratrol inhibited the proliferation of mesangial cells caused by high glucose and down-regulated GSTM and Nrf2 expressions in a dose-dependent manner. These findings suggest that resveratrol help prevent the progression of DN. The renoprotection by resveratrol is in part mediated through the inhibition of high glucose-induced rat mesangial cell proliferation and downregulation of GSTM expression.