ORIGINAL ARTICLE Effects of Stobadine and Vitamin E in Diabetes-Induced Retinal Abnormalities: Involvement of Oxidative Stress Fatma Yu ¨lek, a Meral Or, a Candan O ¨ zo˘ gul, b Asli Ceylan Isik, c Nuray Ari, c Milan Stefek, d Victor Bauer, d and Cimen Karasu e a Department of Ophthalmalogy, b Department of Histology e Medical Pharmacology, Faculty of Medicine, Gazi University, Besevler, Ankara, Turkey c Department of Pharmacology, Faculty of Pharmacy, Ankara University, Tandogan, Ankara, Turkey d Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovak Republic 1 Received for publication November 23, 2006; accepted February 20, 2007 (ARCMED-D-06-00499). Background. Because hyperglycemia-induced oxidative stress may be a cause of retinop- athy, this study examined the hypothesis that administration of exogenous antioxidants, sto- badine (ST) and vitamin E (vitE), can restore retinal abnormalities in experimental diabetes. Methods. Normal and streptozotocin (STZ)-induced male Wistar rats received daily in- traoral doses of ST (24.7 mg/kg) and vitE (a-dl-tocopherol acetate, 400e500 IU/kg) in- dividually or in combinations for 8 months. The biochemical parameters including aldose reductase enzyme (AR) activity and lipid peroxidation (MDA), and histopathological changes such as retinal capillary basement membrane thickness (RCBMT) and vascular endothelial growth factor (VEGF) expression were evaluated. Results. A 37.99% increase in RCBMT was observed in rats after 8 months diabetes du- ration. The increase in RCBMT was 12.34% in diabetic rats treated with ST and 23.07% in diabetic rats treated with vitE. In diabetic rats treated with antioxidant combination, just a 4.38% increase was observed in RCBMT. The excess VEGF immunoreactivity and increased MDA and AR activity determined in diabetic retina were significantly at- tenuated by individual antioxidant treatments. Although both antioxidants decreased blood glucose, HbA1c, fructosamine and triglyceride levels in diabetic rats, poor glyce- mic control was maintained in all experimental groups during the treatment period. How- ever, the antioxidant combination led to almost complete amelioration in retinal MDA and RCBMT in diabetic rats. Conclusions. The ability of antioxidant combination to arrest retinal abnormalities and lipid peroxidation even in the presence of poor glycemic control might advocate the key role of direct oxidative damage and the protective action of antioxidants in retinal alterations associated with diabetic retinopathy. Ó 2007 IMSS. Published by Elsevier Inc. Key Words: Diabetic rat, Stobadine, Vitamin E, Lipid peroxidation, VEGF, Aldose reductase, Retina. Introduction Retinopathy is the most common complication of diabetes mellitus, affecting up to 90% of diabetic patients and pro- gressing to loss of vision in about 5% of cases (1,2). Hyper- glycemia, of course, is the initiating event in the development of retinopathy. However, studies have clearly shown that the oxidative and nitrative modifications in retina occur early in 1 Antioxidants in Diabetes-Induced Complications, The ADIC Study Group. Address reprint requests to: C. Karasu, Department of Medical Phar- macology, Faculty of Medicine, Gazi University, Besevler, Ankara, Turkey; E-mail: karasu@gazi.edu.tr 0188-4409/07 $esee front matter. Copyright Ó 2007 IMSS. Published by Elsevier Inc. doi: 10.1016/j.arcmed.2007.02.006 Archives of Medical Research 38 (2007) 503e511