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Abstract

Volume 14, Issue 4 (July 2012) 14, 616–620; 10.1038/aja.2012.22

The effects of long-term administration of tadalafil on STZ-induced diabetic rats with erectile dysfunction via a local antioxidative mechanism

Yun Chen1, Xiao-Xin Li1, Hao-Cheng Lin1, Xue-Feng Qiu1, Jing Gao2, Yu-Tian Dai1 and Run Wang3

1 Department of Urology, the Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China
2 School of Pharmacy, Jiangsu University, Zhenjiang 212013, China
3 Department of Urology, University of Texas Health Science Center and MD Anderson Cancer Center, Houston, TX 77030, USA

Correspondence: Dr YT Dai, (ytdai@hotmail.com); Dr R Wang, (Run.Wang@uth.tmc.edu)

Received 15 August 2011; Revised 19 October 2011; Accepted 5 December 2011

Abstract

Type 5 phosphodiesterase inhibitors (PDE5Is) are well known being effective via the nitric oxide and cyclic guanosine monophosphate (NO–cGMP) pathway and are widely used in the treatment of diabetic erectile dysfunction (ED). However, it is unclear whether other pathways may be involved in the treatment of diabetic ED with PDE5Is. The purpose of this study was to clarify the role of antioxidants in diabetic ED treatment through the long-term administration of PDE5Is. Three groups of Sprague–Dawley rats were utilized: Group N, the normal control; Group D, streptozotocin (STZ)-induced diabetic rats as a control; and Group D+T, STZ-induced diabetic rats who received oral administration of tadalafil for 8 weeks. Erectile function was assessed by intracavernous pressure (ICP) and mean arterial pressure (MAP) during electrical stimulation of the cavernous nerve before euthanasia. The levels of malondialdehyde (MDA), superoxide dismutase (SOD) and mitochondrial membrane potential (MMP) of cavernous tissue were assessed by biochemical analysis. The morphology of mitochondria was observed by electron microscopy. The ICP/MAP ratio was higher in Group D+T than in Group D (P<0.05). The levels of MDA decreased and the activities of SOD increased in Group D+T in comparison with Group D (P<0.05). The mitochondrial membrane potential level of cavernous tissue in diabetic rats was partially recovered by tadalafil treatment for 8 weeks. The morphology changes of mitochondria were also remarkably ameliorated in Group D+T. Collectively, the long-term administration of tadalafil in diabetic rats partially reduced oxidative stress lesions of the penis via a local antioxidative stress pathway. Long-term dosages of tadalafil given once daily beginning soon after the onset of diabetes may aid in preventing rats from developing diabetic ED.

Keywords: diabetes; erectile dysfunction; mitochondria; oxidative stress; PDE5 inhibitor

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