Separately Administered Phosphodiesterase-5 Inhibitors (Sildenafil and Tadalafil) and Opioid (Tramadol), Reversibly Alter Serum Lipid Profile in Male Albino Wistar Rats

Abstract

Several undesired effects following chronic use of phosphodiesterase-5 inhibitors (particularly, sildenafil and tadalafil) and opioid (tramadol) have been reported. This study assessed the effect of chronic administration of sildenafil, tadalafil, tramadol and sildenafil+tramadol (as used in Nigeria today), on serum lipid profile (cardiovascular risk assessment), since alterations may not be easily discernable by their users. Fifty male albino wistar rats weighing 180-200 g were randomly divided into 5 groups (n = 10), thus; control (0.2 mL normal saline), sildenafil treated (10 mg kgG1), tadalafil treated (10 mg kgG1), tramadol treated (20 mg kgG1) and sildenafil+tramadol treated (10 and 20 mg kgG1, respectively) group. The drugs were administered every two days, per oral route, for eight weeks. All animals had access to food and water ad libitum. At the end of eight weeks, 5 animals were sacrificed from each group, leaving the remaining 5 per group for another 8 weeks without treatment (recovery phase). Blood was collected from each animal via cardiac puncture and serum lipid profile assessed. Serum total cholesterol was significantly (p<0.001) increased in tadalafil treated group, but significantly (p<0.001) reduced in tramadol and sildenafil+tramadol treated groups, compared with control. Serum LDL-c concentration was significantly increased in sildenafil (p<0.01) and tadalafil (p<0.001) treated groups, but significantly reduced in tramadol and sildenafil+tramadol treated groups, compared with control. Cardiac Risk Ratio (CRR) was significantly reduced in tramadol (p<0.001) and sildenafil+tramadol (p<0.01) treated groups, compared with sildenafil and tadalafil treated groups. The same trend was observed for atherogenic coefficient. Atherogenic index of plasma was significantly (p<0.05) reduced in sildenafil+tramadol treated group, compared with control and tadalafil treated groups. Following withdrawal of treatment, serum total cholesterol and LDL-c reduced significantly (p<0.001) in tadalafil recovery group, compared with its treated group, while serum lipid profile did not differ significantly between the treated and recovery group of rats administered sildenafil, tramadol and sildenafil+tramadol. Sildenafil and tadalafil exhibited hyperlipidaemic effects, while tramadol and sildenafil+tramadol exhibited hypolipidaemic effects, with poor reversibility.