title: Ferrous ion supported in vivo lipid peroxidation induced by paracetamol--its relation to hepatotoxicity.
abstract: Treatment of mice with 400 mg/kg paracetamol or 20 mg/kg Fe2+ did not evoke in vivo lipid peroxidation as evidenced by the rate of ethane exhalation. The combined treatment with both, however, led to a more than ninefold enhancement of lipid peroxidation. In glutathione-depleted mice treatment by either agent alone almost doubled the rate of ethane exhalation as compared to the respective control group. Here, again, treatment with both led to an even 26-fold increase in in vivo-lipid peroxidation. These results indicate that iron ions are needed to initiate lipid peroxidation by a redox-cycling metabolite of paracetamol. Marked hepatotoxicity was seen in both groups of mice treated with both Fe2+ and paracetamol as well as in glutathione-depleted mice treated with paracetamol only, the degree of liver damage being identical in all three groups despite of the different rates of lipid peroxidation. This dissociation of hepatotoxic response from ethane exhalation indicates that lipid peroxidation is at least not the sole mechanism by which paracetamol exerts its toxicity towards liver cells.
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D005296:Ferrous Compounds / Q000032:analysis*; D005978:Glutathione / Q000378:metabolism; D007501:Iron / Q000032:analysis*; D008054:Lipid Peroxides / Q000032:analysis*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D013997:Time Factors
chemical_list: D005296:Ferrous Compounds; D008054:Lipid Peroxides; D000082:Acetaminophen; D007501:Iron; D005978:Glutathione