Chronic resveratrol administration improves diabetic cardiomyopathy in part by reducing oxidative stress.

BACKGROUND Based on the key role of hyperglycemia-mediated oxidative stress in the pathogenesis of diabetic cardiomyopathy, increasing antioxidant defense would represent a novel therapeutic approach for management of diabetic cardiomyopathy. This study was designed to seek the effectiveness of chronic treatment with resveratrol, a potent natural antioxidant, on streptozotocin-nicotinamide experimental model of type 2 diabetic hearts. METHODS Male rats randomized into four groups (n = 12): control, diabetic, control + resveratrol, and diabetic + resveratrol. RESULTS Four-month oral resveratrol administration to diabetic rats (5 mg/kg/day) alleviated the reduction of cardiac antioxidant enzymes activities (3.88 ± 0.48 vs. 1.49 ± 0.43 U, p < 0.05 for superoxide dismutase, and 2.72 ± 0.26 vs. 1.18 ± 0.19 nmol/min/mL, p < 0.05 for catalase) and the enhancement of cardiac oxidative markers (5.01 ± 0.37 vs. 7.23 ± 0.51 ng, p < 0.05 for 8-isoprostane, 6.03 ± 0.87 vs. 8.49 ± 0.52 μmol, p < 0.05 for nitrite/nitrate, and 0.44 ± 0.03 vs. 0.59 ± 0.04, p < 0.05 for oxidized/reduced glutathione ratio), nuclear factor kappa B activity (0.37 ± 0.09 vs. 0.60 ± 0.11, p < 0.05) and apoptosis rate (0.98 ± 0.28 vs.1.63 ± 0.16, p < 0.05). Moreover, it improved left ventricular developed pressure (72.46 ± 8.16 vs. 52.01 ± 11.32 mm Hg, p < 0.05) and coronary flow (14.08 ± 1.09 vs. 11.75 ± 1.43 mL/min × g, p < 0.05). CONCLUSIONS These beneficial cardioprotective observations suggest that treatment with resveratrol can potentially delay or attenuate the progression of diabetes-related cardiac complications.