Guinea pig and rat hepatic microsomal metabolism of monocrotaline

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

Research output: Contribution to journalArticle

42 Citations (Scopus)

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

Fingerprint

Monocrotaline
Metabolism
Pyrrolizidine Alkaloids
Rats
Guinea Pigs
Esterases
Metabolites
Liver
Colorimetric analysis
Carboxylic Ester Hydrolases
Carbon Monoxide
Cytochrome P-450 Enzyme System
Toxicity
Hydrolysis
Microsomes
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

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.

Guinea pig and rat hepatic microsomal metabolism of monocrotaline. / Dueker, S. R.; Lame, M. W.; Morin, D.; Wilson, Dennis W; Segall, H. J.

In: Drug Metabolism and Disposition, Vol. 20, No. 2, 1992, p. 275-280.

Research output: Contribution to journalArticle

Dueker, SR, Lame, MW, Morin, D, Wilson, DW & Segall, HJ 1992, 'Guinea pig and rat hepatic microsomal metabolism of monocrotaline', Drug Metabolism and Disposition, vol. 20, no. 2, pp. 275-280.
Dueker, S. R. ; Lame, M. W. ; Morin, D. ; Wilson, Dennis W ; Segall, H. J. / Guinea pig and rat hepatic microsomal metabolism of monocrotaline. In: Drug Metabolism and Disposition. 1992 ; Vol. 20, No. 2. pp. 275-280.
@article{b470200cadf341f6bec152b1a03acc9a,
title = "Guinea pig and rat hepatic microsomal metabolism of monocrotaline",
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.",
author = "Dueker, {S. R.} and Lame, {M. W.} and D. Morin and Wilson, {Dennis W} and Segall, {H. J.}",
year = "1992",
language = "English (US)",
volume = "20",
pages = "275--280",
journal = "Drug Metabolism and Disposition",
issn = "0090-9556",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "2",

}

TY - JOUR

T1 - Guinea pig and rat hepatic microsomal metabolism of monocrotaline

AU - Dueker, S. R.

AU - Lame, M. W.

AU - Morin, D.

AU - Wilson, Dennis W

AU - Segall, H. J.

PY - 1992

Y1 - 1992

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0026529577&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026529577&partnerID=8YFLogxK

M3 - Article

C2 - 1352221

AN - SCOPUS:0026529577

VL - 20

SP - 275

EP - 280

JO - Drug Metabolism and Disposition

JF - Drug Metabolism and Disposition

SN - 0090-9556

IS - 2

ER -