The aim of the study was to investigate the effects of grape seed extract (GSE) supplementation on oxidative stress and antioxidant defense markers in diabetic rats.

The study protocol was approved by Ethics Committee of Experimental Medicine Research and Application Center, Selçuk University. Thirty-seven adult male Sprague-Dawley rats weighing 200-300 g were used. Rats were housed cages with 12/12 h light/dark cycle at 21±2 ^oC and 50% humidity. Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 50 mg.kg^-1 body weight). On the 7^th day after administration of STZ, diabetes was confirmed by measuring blood glucose levels using a glucometer. Rats with blood glucose level 300 mg.dl^-1 or higher considered to be diabetic. Four groups were formed: Control (C, n=8), GSE supplemented control (GC, n=10), diabetic (D, n=6) and GSE supplemented diabetic (GD, n=7). Beginning on the 7^th day after STZ injection the rats in GC and GD groups were administered GSE (100 mg.kg.day^-1) in drinking water for 6 weeks. At the end of the 6^th week, rats were sacrificed by cardiac puncture. Plasma separated from the blood were stored at -80 ordm;C until the time of analysis of malondialdehyde (MDA), xanthine oxidase (XO), adenosine deaminase (ADA), nitric oxide (NO), superoxide dismutase (SOD) and glutathione peroxidase (GPx).

GSE supplementation did not affect blood glucose levels in diabetic rats. Plasma MDA levels increased in diabetic rats and GSE supplementation ameliorated this elevation. XO and ADA activities were higher in diabetic rats compared to other groups. Plasma NO levels decreased in diabetic rats and GSE supplementation normalized that decrease. Antioxidant enzyme activities (SOD and GPx) decreased in diabetic rats compared to the controls. GSE supplementation increased antioxidant enzyme activities both diabetic and healthy rats.

In conclusion, 6 weeks of oral grape seed extract supplementation prevents oxidative stress and improves antioxidant status in diabetic rats.