Document Detail


Hepatic glutathione concentrations and the release of pyrrolic metabolites of the pyrrolizidine alkaloid, monocrotaline, from the isolated perfused liver.
MedLine Citation:
PMID:  1440625     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
L Nigra; R J Huxtable
Related Documents :
6750245 - Prostacyclin production of the isolated pulsatingly perfused rat aorta.
3709065 - Tubular reabsorption rates for myoglobin in the isolated perfused rat kidney.
10353545 - Bradykinin metabolism in perfused rat kidney.
2778735 - The specificity of pyrimidine nucleoside transport and metabolism by rat jejunum in vitro.
1409015 - Vasopressin, corticosterone levels, and gastric ulcers during food-restriction stress.
8698425 - Mode of action of three structurally different hypoglycemic agents: a comparative study.
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Toxicon : official journal of the International Society on Toxinology     Volume:  30     ISSN:  0041-0101     ISO Abbreviation:  Toxicon     Publication Date:  1992 Oct 
Date Detail:
Created Date:  1992-12-16     Completed Date:  1992-12-16     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  1307333     Medline TA:  Toxicon     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1195-202     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, College of Medicine, University of Arizona, Tucson 85724.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Benzaldehydes
Bile / chemistry,  metabolism
Glutathione / metabolism*
Liver / metabolism*
Male
Monocrotaline / metabolism*
Perfusion
Pyrroles / metabolism*
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
HL25258/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
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


Previous Document:  Variation and secretion of toxins in gastropod mollusc Niotha clathrata.
Next Document:  Effects induced by bothropstoxin, a component from Bothrops jararacussu snake venom, on mouse and ch...