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Journal Article

Isoniazid and Iproniazid: Activation of Metabolites to Toxic Intermediates in Man and Rat

S. D. Nelson, J. R. Mitchell, J. A. Timbrell, W. R. Snodgrass and G. B. Corcoran III
Science
New Series, Vol. 193, No. 4256 (Sep. 3, 1976), pp. 901-903
Stable URL: http://www.jstor.org/stable/1742282
Page Count: 3

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Topics: Hydrazines, Propane, Metabolites, Liver, Sterols, Microsomes, Metabolism, Cholesterols, Cytochromes, Necrosis
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Isoniazid and Iproniazid: Activation of Metabolites to Toxic Intermediates in Man and Rat
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Abstract

Acetylhydrazine, a metabolite of isoniazid, a widely used antituberculosis drug, and isopropylhydrazine, a metabolite of iproniazid, an antidepressant removed from clinical use because of high incidence of liver injury, were oxidized by cytochrome P-450 enzymes in human and rat liver microsomes to highly reactive acylating and alkylating agents. Covalent binding of these metabolites to liver macromolecules paralleled hepatic cellular necrosis. The metabolites formed from these and probably other monosubstituted hydrazines are reactive electrophiles.

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