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Research ArticleArticle

ROLE OF DETOXIFYING ENZYMES IN BROMOBENZENE-INDUCED LIVER NECROSIS

N. Zampaglione, D. J. Jollow, J. R. Mitchell, B. Stripp, M. Hamrick and J. R. Gillette
Journal of Pharmacology and Experimental Therapeutics October 1973, 187 (1) 218-227;
N. Zampaglione
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D. J. Jollow
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J. R. Mitchell
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B. Stripp
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M. Hamrick
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J. R. Gillette
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Abstract

The mechanism of 3-methylcholanthrene (3-MC)-induced protection from bromobenzene's hepatotoxicity has been investigated. Determination of the metabolic half-life of bromobenzene indicated that 3-MC induction did not alter the rate of metabolism of bromobenzene in vivo. In contrast, phenobarbital and SKF 525A treatments, which enhance and block, respectively, bromobenzene-induced liver necrosis, enhanced and blocked bromobenzene metabolism. Measurement of bromobenzene metabolism in vitro indicated that 3-MC caused a modest induction of metabolism. Thus 3-MC-induced protection, unlike the SKF 525A effect, is not due to an inhibition of bromobenzene metabolism. Determination of the urinary metabolites of bromobenzene indicated that 3-MC induction caused an increased excretion of bromophenyldihydrodiol and bromocatechol. These metabolites arise from epoxide hydrase-catalyzed hydration of bromobenzene epoxide, suggesting that 3-MC protection is due to an increased capacity to detoxify the chemically highly reactive epoxide. In addition, 2-bromophenol was found to be a major urinary metabolite of hromobenzene in 3-MC-induced rats, suggesting that 3-MC induction may also divert bromobenzene metabolism into a comparatively nontoxic pathway.

Footnotes

    • Received June 29, 1972.
    • Accepted May 31, 1973.
  • © 1973 by The Williams & Wilkins Company

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Journal of Pharmacology and Experimental Therapeutics
Vol. 187, Issue 1
1 Oct 1973
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Research ArticleArticle

ROLE OF DETOXIFYING ENZYMES IN BROMOBENZENE-INDUCED LIVER NECROSIS

N. Zampaglione, D. J. Jollow, J. R. Mitchell, B. Stripp, M. Hamrick and J. R. Gillette
Journal of Pharmacology and Experimental Therapeutics October 1, 1973, 187 (1) 218-227;

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Research ArticleArticle

ROLE OF DETOXIFYING ENZYMES IN BROMOBENZENE-INDUCED LIVER NECROSIS

N. Zampaglione, D. J. Jollow, J. R. Mitchell, B. Stripp, M. Hamrick and J. R. Gillette
Journal of Pharmacology and Experimental Therapeutics October 1, 1973, 187 (1) 218-227;
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