Protective effects of thymoquinone and desferrioxamine against hepatotoxicity of carbon tetrachloride in mice

Abstract

The effects of thymoquinone (TQ) and desferrioxamine (DFO) against carbon tetrachloride (CCU)-induced hepatotoxicity were investigated. A single dose of CCU (20 ul/kg, i.p.) induced hepatotoxicity, manifested biochemically by significant elevation of activities of serum enzymes, such as alanine transaminase (ALT, EC: 2.6.1.2 ) , aspartate transaminase (AST, EC: 2.6.1.1 ) and lactate dehydrogenase (LDH, EC: 1.1.1.27). Hepatotoxicity was further evidenced by significant decrease of total sulfhydryl (-SH) content, and catalase (EC: 1.11.1.6) activity in hepatic tissues and significant increase in hepatic lipid peroxidation measured as malondialdhyde (MDA). Pretreatment of mice with DFO (200 mg/kg i.p.) 1 h before CCU injection or administration of TQ (16 mg/kg/day, p.o.) in drinking water, starting 5 days before CCU injection and continuing during the experimental period, ameliorated the hepatotoxicity induced by CCI4, as evidenced by a significant reduction in the elevated levels of serum enzymes as well as a significant decrease in the hepatic MDA content and a significant increase in the total sulfhydryl content 24 h after CCU administration. In a separate in vitro assay, TQ and DFO inhibited the non-enzymatic lipid peroxidation of normal mice liver homogenate induced by Fe3 +/ascorbate in a dose-dependent manner. These results indicate that TQ and DFO are efficient cytoprotective agents against CCU-induced hepotoxicity, possibly through inhibition of the production of oxygen free radicals that cause lipid peroxidation.