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

International Journal of Impotence Research volume 21, pages 348–355 (2009)Cite this article

Abstract

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 × 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 (3–4months 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.

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Acknowledgements

We thank Dr Roger Erickson for his support and assistance with the preparation of the paper. This study was supported by Grants RO1DK075524, T32DK007790 from the NIH.

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Authors and Affiliations

  1. Department of Urology, San Francisco Veterans Affairs Medical Center and University of California at San Francisco, San Francisco, CA, USA

    T Kawakami, S Urakami, H Hirata, Y Tanaka, H Enokida, H Shiina, T Ogishima, T Tokizane, K Kawamoto & R Dahiya

  2. Department of Urology, Toho University Faculty of Medicine, Tokyo, Japan

    T Kawakami, K Nakajima, K Miura & N Ishii

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  1. T Kawakami
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Correspondence to R Dahiya.

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Kawakami, T., Urakami, S., Hirata, H. et al. Superoxide dismutase analog (Tempol: 4-hydroxy-2, 2, 6, 6-tetramethylpiperidine 1-oxyl) treatment restores erectile function in diabetes-induced impotence. Int J Impot Res 21, 348–355 (2009). https://doi.org/10.1038/ijir.2009.28

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