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International Journal of Pharmacology

Year: 2006 | Volume: 2 | Issue: 3 | Page No.: 280-285
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Authors

Sheyda Hoseini

Hadi Esmaily

Azadeh Mohammadirad

Mohammad Abdollahi

Keywords

Research Article

Effects of Sildenafil a Phosphodiesterase 5 Inhibitor on Rat Liver Cell Key Enzymes of Gluconeogenesis and Glycogenolysis

Sheyda Hoseini, Hadi Esmaily, Azadeh Mohammadirad and Mohammad Abdollahi
In the present study, the effects of short-term administration of sildenafil a selective PDE5 inhibitor on serum glucose and hepatic glycogenolysis and gluconeogenesis were examined in rats in vivo. Sildenafil was administered intraperitoneally at doses of 0.5, 1.0 and 5.0 mg kg-1. Two hours post treatment, liver was perfused, removed and homogenized. The activities of the key enzymes of glycogen phosphorylase (GP) and phosphoenolpyruvate carboxykinase (PEPCK) were analyzed in the homogenate. The high dose of sildenafil (5 mg kg-1) caused a significant reduction in serum glucose levels in comparison to control group (94.6±4.7 vs. 121.16±6.05 mg dL-1). The activity of PEPCK remained unchanged when animals were treated with various doses of sildenafil. Interestingly, sildenafil reduced hepatic GP at all doses administered (20.31±1.42, 17.18±1.2, 15.69±1.1 vs. 25.8±1.8 U g-1 liver protein for control group). It is concluded that administration of sildenafil markedly reduces liver glycogenolysis which in turn lowers blood glucose concentration at higher doses. This effect of sildenafil seems to be in relation with its NO mimicking potential and antioxidant properties. The underlying mechanisms involved seem complicated since parallel increase in the activities of GP and PEPCK was not observed.
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