RT Journal Article
SR Electronic
T1 Guinea pig and rat hepatic microsomal metabolism of monocrotaline.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 275
OP 280
VO 20
IS 2
A1 S R Dueker
A1 M W Lamé
A1 D Morin
A1 D W Wilson
A1 H J Segall
YR 1992
UL http://dmd.aspetjournals.org/content/20/2/275.abstract
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.