| Hepatic glutathione concentrations and the release of pyrrolic metabolites of the pyrrolizidine alkaloid, monocrotaline, from the isolated perfused liver. | |
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MedLine Citation:
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PMID: 1440625 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have examined the relationship between the metabolism of the pyrrolizidine alkaloid, monocrotaline, and glutathione concentration in the isolated, perfused rat liver. On perfusion of monocrotaline (300 microM) through the isolated liver, high concentrations (1.1 mM) of its metabolite glutathionyldehydroretronecine are released into bile, while much lower amounts (4.86 microM; 0.05 mumol/g liver) accumulate in the perfusate over a 1 hr perfusion period. Metabolite concentration in both the bile and perfusate increase when the level of monocrotaline perfused is increased to 900 microM. Metabolite release is also elevated in livers pretreated with phenobarbital. Monocrotaline perfusion lowered glutathione concentrations in the liver from 30 min onwards. Livers from animals treated with buthionine sulfoximine or chloroethanol showed much lower glutathione levels after 60 min perfusion. Livers from chloroethanol-treated (but not buthionine sulfoximine-treated) animals showed significantly lower release of pyrroles into the bile on perfusion with monocrotaline, but there is no effect on the rate of build-up of pyrrolic metabolites in the perfusate. We conclude that hepatic glutathione concentrations and the release of pyrrolic metabolites of monocrotaline mutually interact. Exposure of the liver to monocrotaline reduces glutathione concentrations, while marked depletion of liver glutathione concentration leads to a decrease in the release of monocrotaline metabolites. |
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Authors:
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L Nigra; R J Huxtable |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Toxicon : official journal of the International Society on Toxinology Volume: 30 ISSN: 0041-0101 ISO Abbreviation: Toxicon Publication Date: 1992 Oct |
Date Detail:
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Created Date: 1992-12-16 Completed Date: 1992-12-16 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 1307333 Medline TA: Toxicon Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 1195-202 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 Benzaldehydes Bile / chemistry, metabolism Glutathione / metabolism* Liver / metabolism* Male Monocrotaline / metabolism* Perfusion Pyrroles / metabolism* Rats Rats, Sprague-Dawley |
| Grant Support | |
ID/Acronym/Agency:
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HL25258/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Benzaldehydes; 0/Pyrroles; 100-10-7/4-(dimethylamino)benzaldehyde; 315-22-0/Monocrotaline; 70-18-8/Glutathione |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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