Sildenafil citrate abuse [II]: an ultrastructural study of the long-term administration of sildenafil citrate in male albino rats

ABSTRACT

It has been reported that the most affected organs on abusing sildenafil citrate were the testis, retina, brain and heart; and that these changes were dose-and frequency-dependent. This study was set up to elucidate the ultra-structural alterations and hence the mechanism of toxicity in the retinal, cerebral, myocardial and testicular tissues which could result from administration of sildenafil citrate at a dose equivalent to the 100 mg tablet in humans administered at different frequencies. In addition, the study aimed at the assessment of the suitable dose and frequency of administration of the drug. Forty-eight male Wistar albino rats were used; and they were divided into [n=12] negative control group. [n=36] rats received sildenafil citrate by gavage in a dose of 0.008 mg/g rat. This group was subdivided into 3 subgroups [n=12] rats received the dose daily. [n= 12] rats received the dose day after day. [n= 12] rats received the dose once per week. The study extended for 18 weeks. Small portions from the brain, retina, heart and testes were excised and processed for electron microscopic examination. Sildenafil citrate causes histopathological alterations in the brain, retina, heart and testis in a dose-and time-dependent manner. It exerts its pathologic effects partly through persistent dilatation and thickening of t he blood vessel walls of the a forementioned tissues; and partly via direct action on the tissue cells and in particular on the mitochondria and rough endoplasmic reticulum