Testosterone and chronic sildenafil/tadalafil anti-apoptotic role in aged diabetic rats

Abstract

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.