Biotransformation of Bromobenzene to Reactive Metabolites by Isolated Hepatocytes

  • Hjördis Thor
  • Sten-Åke Svensson
  • Pia Hartzell
  • Sten Orrenius
Part of the Advances in Experimental Medicine and Biology book series (AEMB)


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).


Epoxide Hydrolase Reactive Metabolite Glutathione Disulfide Methionine Sulfoximine Inducible Cytochrome 
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Copyright information

© Springer Science+Business Media New York 1982

Authors and Affiliations

  • Hjördis Thor
    • 1
  • Sten-Åke Svensson
    • 1
  • Pia Hartzell
    • 1
  • Sten Orrenius
    • 1
  1. 1.Department of Forensic MedicineKarolinska institutetStockholmSweden

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