Protective effects of thymoquinone and desferrioxamine against hepatotoxicity of carbon tetrachloride in mice.
The effects of thymoquinone (TQ) and desferrioxamine (DFO) against carbon tetrachloride (CCl4)-induced hepatotoxicity were investigated. A single dose of CCl4 (20 microl/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 CCl4 injection or administration of TQ (16 mg/kg/day, p.o.) in drinking water, starting 5 days before CCl4 injection and continuing during the experimental period, ameliorated the hepatotoxicity induced by CCl4, 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 CCl4 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 CCl4-induced hepotoxicity, possibly through inhibition of the production of oxygen free radicals that cause lipid peroxidation.
Mansour
M A
MA
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D016227:Benzoquinones / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D003676:Deferoxamine / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice
D016227:Benzoquinones; D007502:Iron Chelating Agents; D002251:Carbon Tetrachloride; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003676:Deferoxamine; C003466:thymoquinone