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, 68 (1), 160-4

Possible Mechanism of Liver Necrosis Caused by Aromatic Organic Compounds

Possible Mechanism of Liver Necrosis Caused by Aromatic Organic Compounds

B B Brodie et al. Proc Natl Acad Sci U S A.

Abstract

Treatment of rats with phenobarbital, which stimulates the activity of the drug-metabolizing enzymes in the liver, potentiates hepatic necrosis elicited by bromobenzene and a number of other chemically inert halogenated aromatic hydrocarbons. Radioautographic studies indicate that [(14)C]bromobenzene is covalently bound at the sites of necrosis. From these results, it is inferred that the hepatotoxic effects of the halogenated aromatic hydrocarbons are mediated by chemically active metabolites formed in hepatocytes. In accord with this view, a number of aromatic halogenated hydrocarbons are converted by microsomes in vitro to active intermediates which form covalent complexes with glutathione (GSH).

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