The role of iron in the paracetamol- and CCl4-induced lipid peroxidation and hepatotoxicity.
Treatment of non-induced or phenobarbital-induced, glutathione-depleted mice with 400 mg/kg paracetamol led to a marked ethane exhalation as an index of in vivo lipid peroxidation (LPO) and to a significant elevation of liver-specific serum enzyme activities. Similar effects were seen with rats treated with 0.5 ml/kg CCl4. Pretreatment with the iron-chelating agent desferrioxamine (DFO) clearly suppressed lipid peroxidation in all cases, but inhibited only the CCl4-induced hepatotoxicity. Treatment of mice with desferrioxamine alone showed no hepatotoxicity at all, nor did it influence liver GSH-levels. In addition, DFO had no effect on hepatic microsomal enzyme activities responsible for the bioactivation of both paracetamol and CCl4. These findings are consistent with the theories which indicate that lipid peroxidation requires the presence of Fe2+-ions, regardless of the initiating agent, and that LPO is involved in CCl4-toxicity, but most probably not in paracetamol-induced liver damage. Furthermore, Fe2+-ions might play a role as mediators of CCl4-hepatotoxicity.
D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D001944:Breath Tests; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D003676:Deferoxamine / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004980:Ethane / Q000032:analysis; D007501:Iron / Q000502:physiology*; D008054:Lipid Peroxides / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D008054:Lipid Peroxides; D000082:Acetaminophen; D002251:Carbon Tetrachloride; D007501:Iron; D003676:Deferoxamine; D004980:Ethane; D010634:Phenobarbital