Anti‐oxidative effect of the β‐blocker carvedilol on diabetic nephropathy in non‐obese type 2 diabetic rats

Summary Oxidative stress plays an important role in the pathogenesis of diabetic nephropathy. The β ‐blocker carvedilol has been proven to have an anti‐oxidant property. The aim of the present study was to elucidate the effects of carvedilol on diabetic nephropathy. At 20 weeks of age, male Spontaneously Diabetic Torii ( SDT ) rats were divided into three groups based on treatment: (i) an INS group (administered insulin); (ii) a CAR group (administered 10 mg/kg per day, p.o., carvedilol); and (iii) a diabetic ( DM ) group (administered vehicle). Rats were treated for a period of 10 weeks and were killed at 30 weeks of age. Urinary albumin excretion, renal histomorphology, and oxidative stress were evaluated. Urinary albumin excretion was significantly lower in the CAR than DM group (42.82 ± 3.94 vs 76.62 ± 13.74 mg/day respectively; P < 0.05). The mesangial index was lower in the CAR group than in the DM group. Urinary excretion of 8‐hydroxydeoxyguanosine (8‐ OH dG), the number of 8‐ OH dG‐positive cells in glomeruli, and the mRNA expression of NADPH oxidase p22 phox and p47 phox were also lower in the CAR than DM group. However, haemoglobin A1c (HbA1c) and blood pressure levels were comparable between the two groups. The results suggest that carvedilol could prevent the progression of diabetic nephropathy by suppressing oxidative stress.