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

T Mostafa1, L A Rashed, K Kotb

  • 1Department of Andrology and Sexology, Faculty of Medicine, Cairo University, Cairo, Egypt. taymour1155@link.net

International Journal of Impotence Research
|June 25, 2010
PubMed

Insights

Chronic low-dose sildenafil and tadalafil, with or without testosterone, significantly reduced apoptosis in aged diabetic rat cavernous tissues, suggesting a protective effect against diabetic complications.

Area of Science:

  • Urology
  • Endocrinology
  • Pharmacology

Background:

  • Diabetes mellitus is associated with erectile dysfunction due to increased apoptosis in cavernous tissues.
  • Aging exacerbates diabetic complications, including impaired erectile function.
  • Testosterone (T) therapy and phosphodiesterase-5 inhibitors (sildenafil, tadalafil) are used to manage erectile dysfunction.

Purpose of the Study:

  • To investigate the anti-apoptotic effects of chronic low-dose sildenafil and tadalafil, alone or combined with testosterone, in aged diabetic rats.
  • To evaluate the impact of these treatments on apoptotic and anti-apoptotic factors in cavernous tissue.
  • To determine the potential therapeutic benefits for diabetic-associated erectile dysfunction.

Main Methods:

  • 140 aged Sprague-Dawley rats were divided into control, diabetic, and various treatment groups (T, sildenafil, tadalafil, combinations).
  • Treatments included intramuscular T, daily oral sildenafil, every-other-day oral tadalafil, and alternating regimens, with or without T, for 12 weeks.
  • Cavernous tissues were analyzed for Bax (apoptotic marker), Bcl-2 (anti-apoptotic marker), and cGMP levels.

Main Results:

  • Diabetic rats exhibited increased Bax and decreased Bcl-2 levels compared to controls.
  • Testosterone treatment reversed these changes in diabetic rats.
  • Sildenafil and tadalafil significantly increased Bcl-2 and decreased Bax, improving the Bcl-2/Bax ratio, with further enhancement when combined with T.
  • Alternating sildenafil/tadalafil regimens, with or without T, further increased Bcl-2 and the Bcl-2/Bax ratio.

Conclusions:

  • Chronic low-dose sildenafil and/or tadalafil demonstrate significant anti-apoptotic effects in the cavernous tissue of aged diabetic rats.
  • Combination therapy with testosterone enhances these protective effects.
  • These findings suggest a potential therapeutic strategy for managing diabetic-associated erectile dysfunction by reducing cavernous tissue apoptosis.

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