title: [The significance of lipid peroxidation in drug-induced liver damage].
abstract: Using the primary hepatotoxin paracetamol (acetaminophen) as a model it is shown in vivo in the mouse that the phase I metabolism of this agent causes a dose-dependent lipid peroxidation. This finding is extended to other xenobiotics activated in phase I and becomes manifest only if the glutathione redox systems as an endogenous defense system is paralyzed. The concept of lipid peroxidation being an early causal event in hepatocellular destruction was experimentally examined: Animals with alimentary selenium deficiency lacking glutathione peroxidase activity were much more susceptible to drug overdosage. Animals pretreated with liposomally entrapped reduced glutathione were totally resistant. Using the isolated perfused liver it is demonstrated that lipid peroxidation precedes cell disintegration. These animal data are discussed with respect to the biochemical parameters available for man. The results suggest an involvement of lipid peroxidation in certain acute chemical lesions, but do not justify to derive a general pathogenic concept based on lipid peroxidation.
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008107:Liver Diseases / Q000201:enzymology / Q000378:metabolism; D051379:Mice
chemical_list: D008054:Lipid Peroxides; D000082:Acetaminophen; D005978:Glutathione
vernacular_title: Die Bedeutung der Lipid-Peroxidation beim medikamentös-toxischen Leberschaden.