This laboratory has previously postulated that bromobenzene-induced hepatic necrosis results from the formation of a reactive metabolite that arylates vital cellular macromolecules. Accordingly, the severity of liver necrosis has been compared with the formation of metabolites of bromobenzene and with covalent binding of metabolites in vivo
and in vitro
after various pretreatment regimens that alter hepatotoxicity. These data provide direct kinetic evidence that 3,4-bromobenzene oxide is the reactive hepatotoxic metabolite. The studies also demonstrate that the hepatotoxic metabolite is preferentially conjugated (detoxified) with glutathione, thereby depleting glutathione from the liver. Liver necrosis and arylation of cellular macromolecules occur only when glutathione is no longer available. Thus, a dose threshold exists for bromobenzene-induced hepatic necrosis.
Request reprints from: Dr. David Jollow, Laboratory of Chemical Pharmacology, National Heart and Lung Institute, Bethesda, MD 20014 (USA)
Received: September 24, 1973
Published online: May 28, 2008
Number of Print Pages : 19
Pharmacology (International Journal of Experimental and Clinical Pharmacology)
Vol. 11, No. 3, Year 1974 (Cover Date: 1974)
Journal Editor: Donnerer J. (Graz), Billingsley M.L. (Hershey, Pa.), Maeyama K. (Matsuyama)
ISSN: 0031–7012 (Print), eISSN: 1423–0313 (Online)
For additional information: http://www.karger.com/PHA
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