Abstract
Background: Sildenafil citrate is a phosphodiesterase type 5 (PDE5) inhibitor, which increases cyclic guanosine monophosphate (cGMP). It is well established that the pathogenesis of diabetic mellitus is associated with abnormalities of nitric oxide (NO) generation. Many of the biological actions of NO are mediated by cGMP, which is rapidly degraded by phosphodiesterases.
Aim: The Aim of this study is to evaluate the effect of sildenafil citrate on some biochemical and hematological parameters in alloxan-induced diabetes in male albino rat.
Methods: Diabetes was induced after an intraperitoneal (i.p.) injection of a single dose of alloxan (150 mg/kg body weight). Sildenafil was administered daily at a dose of (10 mg/kg body weigh) via oral gavages during a period of 14 days to normal healthy rats as well as diabetic rats. Blood samples were collected after 7 and 14 days of treatment in all experimental groups.
Results: The present investigation showed that alloxan injection induced significant elevations in serum glucose level, the percent of glycohemoglobin (HbA1c) and serum malondialdehyed (MDA) level. Moreover, alloxan administration resulted in prolongation of prothrombin time (PT), activated partial thromboplastin time (APTT), as well as increase in plasma fibrinogen level. Meanwhile, protein C and protein S concentrations were significantly decreased due to alloxan treatment. Oral administration of sildenafil to diabetic rats improved most diabetic complications including hyperglycemia, oxidative stress, hemoglycation and hyperfibrinogenemia induced by alloxan. The modulatory effects of sildenafil obtained herein were partial, but significant and more pronounced when administered for14 days. In addition, sildenafil administration to normal healthy rats was found to have no effect on the studied parameters.
Conclusion: The present study showed that sildenafil may have beneficial effects against some diabetic complications. The mechanism by which sildenafil citrate exerts its effect on the studied parameters might be attributed to increased cGMP which is brought out by its phosphodiesterase inhibitory action and this is discussed in details.
Key words: Alloxan, Hyperglycemia, Hyperfibrinogenemia, Protein C, Protein S, Sildenafil citrate.
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