| Monocrotaline metabolism and distribution in Fisher 344 and Sprague-Dawley rats. | |
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MedLine Citation:
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PMID: 9180020 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The metabolism and distribution of 14C-monocrotaline in Fisher 344 (F344) rats was compared with that in Sprague-Dawley (SD) rats. In vitro microsomal preparations, in situ isolated perfused livers and in vivo excretion and distribution studies were used to discern any differences between these two strains. These strains have previously been shown to differ in their susceptibility to monocrotaline-induced pulmonary hypertension. Hepatic phase I metabolism appears to be similar in both strains with N-oxidation and dehydrogenation to the reactive pyrroles as the major pathways. During the liver perfusions, SD rats generated more monocrotalic acid than F344 rats, but the microsome and excretion studies demonstrated no significant differences in the amount of monocrotalic acid. Monocrotalic acid is a stable byproducer of dehydromonocrotaline reacting with cellular nucleophiles and indicates the amount of monocrotaline dehydrogenation when carboxylesterase activity is negligible. These data suggest that the differences in strain susceptibility to pulmonary vascular toxicity is most likely due to differences in their response to the toxic metabolites. |
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Authors:
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M J Reid; M W Lamé; D Morin; D W Wilson; H J Segall |
Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology Volume: 117 ISSN: 1096-4959 ISO Abbreviation: Comp. Biochem. Physiol. B, Biochem. Mol. Biol. Publication Date: 1997 May |
Date Detail:
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Created Date: 1997-07-24 Completed Date: 1997-07-24 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9516061 Medline TA: Comp Biochem Physiol B Biochem Mol Biol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 115-23 Citation Subset: IM |
Affiliation:
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Department of Veterinary Medicine and Molecular Biosciences, University of California, Davis 95616, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bile / chemistry Biotransformation Carboxylesterase Carboxylic Ester Hydrolases / metabolism Chromatography, High Pressure Liquid Feces / chemistry Glutathione / metabolism Hypertension, Pulmonary / chemically induced Liver / metabolism* Male Microsomes, Liver / metabolism* Monocrotaline / analogs & derivatives, analysis, metabolism*, toxicity Perfusion Rats Rats, Inbred F344 Rats, Sprague-Dawley Species Specificity Tissue Distribution |
| Chemical | |
Reg. No./Substance:
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315-22-0/Monocrotaline; 70-18-8/Glutathione; EC 3.1.1.-/Carboxylic Ester Hydrolases; EC 3.1.1.1/Carboxylesterase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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