Superoxide dismutase analog (Tempol: 4-hydroxy-2, 2, 6, 6-tetramethylpiperidine 1-oxyl) treatment restores erectile function in diabetes-induced impotence

Abstract

We hypothesized that administration of the superoxide dismutase (SOD) mimetic Tempol (4-hydroxy-2, 2, 6, 6-tetramethylpiperidine 1-oxyl) may reverse diabetes induced ED(erectile dysfunction). To test this hypothesis, ROS related genes (SOD1, SOD2, GPx1, CAT, NOS2, NOS3), erectile functional studies, and immunohistochemical analysis were performed in diabetic rats treated with or without Tempol. Thirty Sprague-Dawley (3–4 months old) rats were divided into 3 groups (n=10 each), 20 with diabetes (diabetic control and Tempol treatment) and 10 healthy controls. Twelve weeks after induction of diabetes by streptozotocin and Tempol treatment, all groups underwent in vivo cavernous nerve stimulation. Rat crura were harvested and expression of antioxidative defense enzymes examined by semi-quantitative RT-PCR. To confirm the RT-PCR results, we performed immunohistochemistry (IHC) for catalase (CAT) and iNOS (NOS2). Nitration of tyrosine groups in proteins was also examined by IHC. Mean intracavernous pressure in the diabetic group was significantly lower than in healthy controls (p<0.001) and was reversed by Tempol treatment (p<0.0108). NOS2 protein expression was significantly increased in diabetic animals compared to healthy controls and Tempol restored NOS2 protein level. Nitrotyrosine was also higher in diabetic animals and though Tempol treatment decreased its formation, it remained higher than that found in healthy controls. This study suggests that Tempol treatment increased erectile function through modulating oxidative stress related genes in diabetic rats. This is the first report about the relationship between diabetes induced erectile dysfunction and oxidative stress, and anti-oxidative therapy using the superoxide dismutase mimetic, Tempol to restore erectile function.