This work aimed to assess the cavernous anti-apoptotic role of using chronic low-dose sildenafil/ tadalafil with and without testosterone (T) in aged diabetic rats. In all, 140 Sprague-Dawley aged rats were divided into the following groups: controls; induced diabetic rats; diabetic rats that received intramuscular depot T once every 4 weeks; diabetic rats on sildenafil 2 mg kg -1 orally daily; diabetic rats on T and daily sildenafil; diabetic rats on tadalafil 0.45 mg kg -1 orally every other day; diabetic rats on every-other-day tadalafil and T; diabetic rats on alternate sildenafil and tadalafil; and diabetic rats on alternate sildenafil, tadalafil and T. After 12 weeks, Bax (apoptotic factor), Bcl 2 (B-cell lymphoma 2; anti-apoptotic factor), cGMP (cyclic guanosine monophosphate) were estimated in their cavernous tissues. Compared with the controls, aged diabetic rats showed significant increased cavernous tissue Bax and significant decreased Bcl 2 , in which diabetic rats injected with T showed the reverse compared with the diabetic rats. Diabetic rats on sildenafil or tadalafil showed significant increased cavernous Bcl 2 and decreased Bax with upgraded Bcl 2 /Bax ratio that was improved being on T. Diabetic rats on alternate sildenafil/tadalafil with or without T showed further significant increased cavernous tissue Bcl 2 with upgraded Bcl 2 /Bax ratio. It is concluded that frequent low-dose use of sildenafil and/or tadalafil combined with T would be predicted to have a pronounced anti-apoptotic cavernous tissue effect on the cavernous tissues of aged diabetic rats.

This study aimed to assess the effect of testosterone (T) administration and chronic low-dose sildenafil/tadalafil on cavernous tissue oxidative stress (OS) of aged diabetic rats. In all, 140 Sprague-Dawley aged rats were subdivided into the following: controls; streptozotocin (STZ)-induced diabetic rats; diabetic rats injected with T every 4 weeks; diabetic rats on sildenafil orally daily; diabetic rats on T and daily sildenafil; diabetic rats on tadalafil orally every other day; diabetic rats on T and tadalafil; diabetic rats on alternate sildenafil/tadalafil; and diabetic rats on alternate sildenafil/tadalafil with T. After 12 weeks, the rats were euthanised where in dissected cavernous tissues malondialdehyde (MAD), glutathione peroxidase (GPx) and cGMP (cyclic guanosine monophosphate) were estimated. Compared with controls, aged diabetic rats demonstrated significant increase in cavernous tissue MDA and significant decrease in GPx and cGMP where diabetic rats injected with T had marked improvement of these parameters. Diabetic rats on sildenafil, tadalafil or alternate sildenafil/tadalafil demonstrated significant increased cavernous tissue GPx, cGMP and decreased cavernous MDA that was further improved when supplemented with T. It is concluded that frequent low-dose use of sildenafil and/or tadalafil supplemented with T has a marked impact on ameliorating cavernous OS in aged diabetic rats.