Oxidative metabolism of some hydrazine derivatives by rat liver and lung tissue fractions.

John M Erikson, R. A. Prough

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The enzyme systems in rat liver and lung responsible for the oxidative metabolism of hydrazine derivatives were studied to determine whether these enzymes, cytochrome P-450 and monoamine oxidase, were responsible for metabolically activating hydrazines to carcinogenic/toxic metabolites. Cytochrome P-450 preferentially oxidized the nitrogen to nitrogen bond of 1,2-disubstituted hydrazines and hydrazides, while monoamine oxidase oxidized the nitrogen to nitrogen bond of all the classes of hydrazine derivatives that were tested. Oxidation of the nitrogen to nitrogen bond led to the formation of stable azo intermediates in the case of 1,2-disubstituted hydrazines and to unstable monoazo (diazene) metabolites in the case of monosubstituted hydrazines and hydrazides. In addition, cytochrome P-450 preferentially oxidized the carbon to nitrogen bond of monoalkylhydrazines; this reaction resulted in the formation of aldehyde metabolites (via hydrazone intermediates). Monosubstituted hydrazines were shown to be potent, irreversible inhibitors of mitochondrial monoamine oxidase. In contrast, the 1,2-disubstituted hydrazines appeared to be good substrates for the monoamine oxidase and served as competitive inhibitors at high concentrations. There did not appear to be any monoamine oxidase isozyme (form A or B) specificity in the metabolism of either the 1,2-disubstituted hydrazines or the monoalkylhydrazines, ethyl- and n-propylhydrazine.

Original languageEnglish (US)
Pages (from-to)41-52
Number of pages12
JournalJournal of Biochemical Toxicology
Volume1
Issue number1
StatePublished - Mar 1986
Externally publishedYes

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hydrazine
Hydrazines
Metabolism
Liver
Rats
Nitrogen
Monoamine Oxidase
Tissue
Derivatives
Lung
Metabolites
Cytochrome P-450 Enzyme System
Hydrazones
NADPH-Ferrihemoprotein Reductase
Monoamine Oxidase Inhibitors
Poisons
Enzymes
Aldehydes
Isoenzymes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Oxidative metabolism of some hydrazine derivatives by rat liver and lung tissue fractions. / Erikson, John M; Prough, R. A.

In: Journal of Biochemical Toxicology, Vol. 1, No. 1, 03.1986, p. 41-52.

Research output: Contribution to journalArticle

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