Olorunfemi R Molehin1, Anne A Adeyanju2, Stephen A Adefegha3, Oluwasanmi O Aina4, Blessing A Afolabi5, Ayorinde O Olowoyeye6, Jesutomi A Oyediran6, Opeyemi R Oladiran6. 1. Department of Biochemistry, Faculty of Science, Ekiti State University, Ado-Ekiti. P.M.B.5363, Ado-Ekiti, Nigeria, Phone: +234 803 462 1267, E-mail: molehin.olorunfemi@gmail.com. 2. Department of Biological Sciences, McPherson University, Seriki Sotayo, Ajebo, Nigeria. 3. Functional Foods and Nutraceuticals Unit, Department of Biochemistry, Federal University of Technology, Akure, Nigeria. 4. Department of Veterinary Anatomy, University of Ibadan, Ibadan, Nigeria. 5. Department of Biochemistry, Bowen University, Iwo, Nigeria. 6. Department of Biochemistry, Faculty of Science, Ekiti State University, Ado-Ekiti. P.M.B.5363, Ado-Ekiti, Nigeria.
Abstract
BACKGROUND: Elevation of phosphodiesterase-5 (PDE5) activity converts cyclic guanosine monophosphate (cGMP) to 5'-GMP, a mechanism that could be associated with drug-mediated hepatotoxicity. This study investigated whether selective inhibition of PDE5 by sildenafil could offer protection against hepatotoxicity induced by carbon tetrachloride (CCl4). METHODS: CCl4 (0.5 mL/kg) was administered intraperitoneally to induce hepatotoxicity. The control group received normal saline. Sildenafil (5 mg, 10 mg, and 20 mg/kg, p.o.) was administered to CCl4-treated rats. RESULTS: CCl4 significantly increased the serum levels of gamma glutamyl transferase (γ-GT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) and reduced total protein (TP) (p<0.05). Pretreatment with sildenafil moderately reduced ALP, AST, and ALT activities with modest increase in TP level. CCl4-induced changes in the antioxidant status of the liver were significantly improved by sildenafil, especially at the lowest dose of 5 mg/kg by elevating the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and glutathione-S-transferase (GST) and preventing lipid peroxidation (p<0.05). Sildenafil did not significantly alter the total cholesterol and triglyceride levels. However, high-density lipoprotein (HDL) level was significantly increased by sildenafil (p<0.05). CONCLUSIONS: The results from this study suggest that sildenafil, when used at low doses, may be a useful pharmacological protective agent against CCl4-induced hepatotoxicity.
BACKGROUND: Elevation of phosphodiesterase-5 (PDE5) activity converts cyclic guanosine monophosphate (cGMP) to 5'-GMP, a mechanism that could be associated with drug-mediated hepatotoxicity. This study investigated whether selective inhibition of PDE5 by sildenafil could offer protection against hepatotoxicity induced by carbon tetrachloride (CCl4). METHODS:CCl4 (0.5 mL/kg) was administered intraperitoneally to induce hepatotoxicity. The control group received normal saline. Sildenafil (5 mg, 10 mg, and 20 mg/kg, p.o.) was administered to CCl4-treated rats. RESULTS:CCl4 significantly increased the serum levels of gamma glutamyl transferase (γ-GT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) and reduced total protein (TP) (p<0.05). Pretreatment with sildenafil moderately reduced ALP, AST, and ALT activities with modest increase in TP level. CCl4-induced changes in the antioxidant status of the liver were significantly improved by sildenafil, especially at the lowest dose of 5 mg/kg by elevating the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and glutathione-S-transferase (GST) and preventing lipid peroxidation (p<0.05). Sildenafil did not significantly alter the total cholesterol and triglyceride levels. However, high-density lipoprotein (HDL) level was significantly increased by sildenafil (p<0.05). CONCLUSIONS: The results from this study suggest that sildenafil, when used at low doses, may be a useful pharmacological protective agent against CCl4-induced hepatotoxicity.