| Quantitation of the hepatic release of metabolites of the pyrrolizidine alkaloid, monocrotaline. | |
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MedLine Citation:
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PMID: 8048054 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Pyrrolizidine alkaloids such as monocrotaline are bioactivated in the liver to pneumotoxins that cause pulmonary arterial hypertension and right ventricular hypertrophy. The release of the highly reactive, alkylating pyrrole, dehydromonocrotaline, from the isolated rat liver perfused with monocrotaline has now been demonstrated and quantified, using thiopropyl Sepharose resin as a trapping agent. The isolated liver extracted 55% of the alkaloid over the course of a 1-hr perfusion with 0.5 mM monocrotaline. Of the total monocrotaline perfused, 0.4% was excreted into bile and 7.6% was detectable as pyrrolic metabolites. Of these metabolites, 156 nmol/g liver appeared in the bile as glutathionyldehydroretronecine, with the average concentration in bile being 3.53 mM. The perfusion medium at the end of the perfusion contained 113 nmol/g liver of the two pyrroles, dehydroretronecine and glutathionyldehydroretronecine. Remaining in the liver was 56 nmol/g of tissue-bound pyrroles. Over the course of a 1-hr perfusion, 88 nmol/g liver of dehydromonocrotaline was released into the perfusate, as determined by trapping with thiopropyl Sepharose, a resin that reacts only with alkylating pyrroles. This establishes that dehydromonocrotaline is released on perfusing the isolated liver with monocrotaline. The amount released under these conditions is equivalent to 1.08 +/- 0.06 mg/kg body weight, which can be compared to the intravenous dose of 4.85 mg/kg body weight of dehydromonocrotaline found by others to be a pneumotoxic dose. |
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Authors:
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C C Yan; R J Huxtable |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Toxicology and applied pharmacology Volume: 127 ISSN: 0041-008X ISO Abbreviation: Toxicol. Appl. Pharmacol. Publication Date: 1994 Jul |
Date Detail:
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Created Date: 1994-08-30 Completed Date: 1994-08-30 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0416575 Medline TA: Toxicol Appl Pharmacol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 58-63 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, College of Medicine, University of Arizona, Tucson 85724. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bile / metabolism Chromatography, Thin Layer Liver / metabolism* Male Monocrotaline / analogs & derivatives*, metabolism* Rats Rats, Sprague-Dawley |
| Grant Support | |
ID/Acronym/Agency:
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HL-25258/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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23291-96-5/monocrotaline pyrrole; 315-22-0/Monocrotaline |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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