We hypothesized that the administration of the
superoxide dismutase (SOD) mimetic
Tempol (4-hydroxy-2, 2, 6, 6-tetramethylpiperidine 1-oxyl) may reverse diabetes-induced
erectile dysfunction. To test this hypothesis,
reactive oxygen species-related genes (SOD1, SOD2, GP x 1, CAT, NOS2, NOS3) were tested, erectile functional studies and immunohistochemical analysis were carried out in diabetic rats treated with or without
Tempol. Thirty Sprague-Dawley (3-4 months old) rats were divided into three groups (n=10 each), 20 with diabetes (diabetic control and
Tempol treatment) and 10 healthy controls. At 12 weeks after the induction of diabetes by
streptozotocin and
Tempol treatment, all groups underwent in vivo cavernous nerve stimulation. Rat crura were harvested and the expression of antioxidative defense
enzymes were examined by semi-quantitative
reverse transcriptase PCR (RT-PCR). To confirm the RT-PCR results, we carried out 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 the healthy controls (P <0.001) and was reversed by
Tempol treatment (P <0.0108). NOS2
protein expression was significantly increased in diabetic animals compared with healthy controls and
Tempol restored NOS2
protein level.
Nitrotyrosine was also higher in diabetic animals and although
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 antioxidative
therapy using the
superoxide dismutase mimetic,
Tempol, to restore erectile function.