Biotransformation of Bromobenzene to Reactive Metabolites by Isolated Hepatocytes
Bromobenzene is a widely studied hepatotoxic agent which produces midzonal liver necrosis when administered in sufficient doses to laboratory animals (Koch-Weser et al., 1953; Reid et al., 1971). Metabolic activation of bromobenzene to reactive intermediate(s) by the cytochrome P-450-linked monooxygenase system is required for this agent to produce liver damage which, in turn, is preceded by depletion of hepatic glutathione (GSH) (Jollow et al., 1974; Thor et al., 1978b). Accordingly, the hepatotoxic effect of bromobenzene is enhanced by either induction of the cytochrome P-450 system or lowering of hepatic glutathione level by pretreatment of the animals with GSH-depleting agents. Conversely, hepatotoxicity is prevented by simultaneous administration of cytochrome P-450 inhibitors and is also counteracted by the stimulated glutathione biosynthesis resulting from administration of certain glutathione precursors (Mitchell et al., 1971; Thor et al., 1979).
KeywordsEpoxide Hydrolase Reactive Metabolite Glutathione Disulfide Methionine Sulfoximine Inducible Cytochrome
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