Guinea pig and rat hepatic microsomal metabolism of monocrotaline

S. R. Dueker, M. W. Lame, D. Morin, Dennis W Wilson, H. J. Segall

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42 Scopus citations

Abstract

The comparative metabolism of the pyrrolizidine alkaloid, [14C]monocrotaline, was studied using rat and guinea pig hepatic microsomes. Metabolites were quantified to the nanomole level using HPLC and radiometric detection. Triorthocresylphosphate and carbon monoxide were used to assess the involvement of carboxylesterases and cytochrome P-450 in the hepatic microsomal metabolism of monocrotaline, respectively. Esterase hydrolysis accounted for 92% of the metabolism in the guinea pig; the rat displayed no esterase activity. This result may explain the guinea pig's resistance to pyrrolizidine alkaloid toxicity. Dehydropyrrole was found to be the major pyrrolic metabolite in the guinea pig, although colorimetric analysis indicated multiple pyrrolic moieties in the rat microsomal incubations.

Original languageEnglish (US)
Pages (from-to)275-280
Number of pages6
JournalDrug Metabolism and Disposition
Volume20
Issue number2
StatePublished - 1992

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

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    Dueker, S. R., Lame, M. W., Morin, D., Wilson, D. W., & Segall, H. J. (1992). Guinea pig and rat hepatic microsomal metabolism of monocrotaline. Drug Metabolism and Disposition, 20(2), 275-280.