ED 06. The long-term administration of tadalafil on STZ - induced diabetic rats with erectile dysfunction via local antioxidative mechanism

Introduction: Type 5 phosphodiesterase inhibitor (PDE5I) that is well-known effective via NO-cGMP pathway is widely used in diabetic erectile dysfunction (ED). Whether there is any other mechanism of PDE5I treatment in diabetic ED that is not clear.

Aim: To clarify the antioxidation role in diabetic ED treatment by a long-term administration of PDE5I.

Methods: Three groups of Sprague-Dawley rats were utilized: Group N: Normal control; Group D: Streptozotocin (STZ) induced diabetic rats as control; Group D+T: STZ induced diabetic rats by the intragastric administration with tadalafil for eight weeks.

Main outcome measures: Erectile function was assessed by intracavernous pressure (ICP) and mean arterial pressure (MAP) during electrical stimulation of cavernous nerve before sacrifice. 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.

Results: ICP/MAP ratio was significantly higher in Group D+T than in Group D. The levels of MDA decreased remarkably and the activities of SOD increased significantly of Group D+T, compared with Group D. The level of mitochondrial membrane potential of cavernous tissue of diabetic rats was partly recovered by tadalafil treatment for eight weeks. The morphology changes of mitochondria were also ameliorated in Group D+T.

Conclusions: The long-term administration of tadalafil on diabetic rats is proven to partly lessen the oxidative stress lesion of the penis via a local antioxidative stress pathway. Early long-term dosages of tadalafil once daily maybe partly prevent rats from diabetic erectile dysfunction. To our knowledge, this is the first report to reveal the new mechanism on long-term treatment of tadalafil in diabetic ED.