Sildenafil, a phosphodiesterase-5 inhibitor, offers protection against carbon tetrachloride-induced hepatotoxicity in rat.

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.

White butterfly (Clerodendrum volubile) leaf extract protects against carbon tetrachloride-induced hepatotoxicity in rats.

Currently, there is increasing attention towards flavonoids and phenolic compounds of plant origin because of their association with decrease in the incidence of cardiovascular diseases and different types of cancer. The present study investigates the protective effect of Clerodendrum volubile (C. volubile) methanolic extracts against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Control rats (group I) received olive oil (1 mL/kg, i.p.), group II received CCl4 in olive oil (1 ml/kg, i.p.) to induce hepatotoxicity, groups III, IV and V were pretreated with leaf extract of C. volubile at 125 mg/kg, 250 mg/kg and 500 mg/kg body weight respectively for 14 days prior to CCl4 administration, group VI received vitamin E (100 mg/kg, p.o.) as standard antioxidant to compare with antioxidant effects of the extract. CCl4 hepatotoxicity, characterized by significant (P < 0.05) increase in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), hepatic degeneration, and inflammation was attenuated by C. volubile methanolic extracts. The serum lipid parameters which include high density lipoprotein (HDL) and low density lipoprotein (LDL) were significantly (P < 0.05) decreased, and increased respectively by CCl4. Methanolic extracts of C. volubile significantly prevented the decrease in the level of HDL and the increase in LDL in a dose-dependent manner (P < 0.05). Decrease in total protein induced by CCl4 was moderately increased following administration of methanolic extracts of C. volubile. Lipid peroxidation was significantly (P < 0.05) reduced while the reduced glutathione (GSH) level and the activities of hepatic antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) were significantly elevated by C. volubile extract in the CCl4-treated rats. Our findings indicate that C. volubile extract has a significant protective effect against CCl4-induced hepatotoxicity in rats which may be due to its antioxidant properties which is comparable to the reference antioxidant, vitamin E, used in this study.