Effect of obtusifolin administration on retinal capillary cell death and the development of retinopathy in diabetic rats.

Abstract

Oxidative stress is increased in the retina in diabetes, and it is considered to play an important role in the development of retinopathy. Findings indicate that obtusifolin has antioxidant properties. The purpose of this study was to examine the effect of obtusifolin on retinal capillary cell apoptosis and the development of pathology in diabetes. Retina was used from streptozotocin-induced diabetic rats receiving diets supplemented with or without obtusifolin (100, 200, and 400 mg/kg) for 11 months of diabetes. Capillary cell apoptosis (by terminal transferase-mediated dUTP nick-end labeling) and formation of acellular capillaries were investigated in the trypsin-digested retinal microvessels. The effect of obtusifolin administration on retinal 8-hydroxy-2'deoxyguanosine (8-OHdG) and nitrotyrosine levels was determined by enzyme-linked immunosorbent assay. Obtusifolin administration for the entire duration of diabetes inhibited capillary cell apoptosis and the number of acellular capillaries in the retina, despite similar severity of hyperglycemia in the four diabetic groups (with and without obtusifolin). Retinal 8-OHdG and nitrotyrosine levels were significantly increased, respectively, in diabetes, and obtusifolin administration inhibited these increases. Our results demonstrate that the long-term administration of obtusifolin has beneficial effects on the development of diabetic retinopathy via inhibition of accumulation of oxidatively modified DNA and nitrotyrosine in the retina. Obtusifolin represents an achievable adjunct therapy to help prevent vision loss in diabetic patients.