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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1992-9-18
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pubmed:abstractText |
The aim of the present study was to introduce and validate a radioactive tracer method in which adenosine 3'-phosphate 5'-phosphosulfate (PAPS) and glutathione (GSH) are measured simultaneously in isolated hepatocytes. PAPS and GSH are co-substrates in sulphation and GSH conjugation, and both are dependent on sulphur deriving from cysteine. The effect of cysteine on the syntheses was investigated at non-toxic and toxic concentrations of the hepatotoxic drug acetaminophen (AA). Administration of AA trapped radioactivity (35S) in the pre-labelled PAPS and GSH pools by formation of the metabolites, AA-sulphate and AA-GSH. Turnover rates were determined from the decline of AA-sulphate and AA-GSH specific activity. Syntheses of PAPS and GSH were calculated by multiplying the rates with the concentrations of the respective co-substrates. Increasing AA concentration from non-toxic to toxic levels resulted in increased median PAPS and GSH syntheses (8 to 11 and 311 to 2218 nmol/10(6) cells/min, respectively) (P less than 0.05). Addition of cysteine did not alter median PAPS synthesis (5 to 3 nmol/10(6) cells/min) but decreased median GSH synthesis (666 to 261 nmol/10(6) cells/min) (P less than 0.05) in experiments with non-toxic AA concentrations. In experiments with toxic AA concentrations opposite effects of cysteine were seen, i.e. median PAPS synthesis was reduced (3 to 2 nmol/10(6) cells/min) (P less than 0.05) while median GSH synthesis was unchanged (23 to 16 nmol/10(6) cells/min). The present method provides a tool in which two important detoxification pathways can be measured simultaneously and the data suggest that the two pathways are regulated by substrate availability.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0006-2952
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
4
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pubmed:volume |
44
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
447-54
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:1510695-Acetaminophen,
pubmed-meshheading:1510695-Animals,
pubmed-meshheading:1510695-Cysteine,
pubmed-meshheading:1510695-Female,
pubmed-meshheading:1510695-Glutathione,
pubmed-meshheading:1510695-Liver,
pubmed-meshheading:1510695-Phosphoadenosine Phosphosulfate,
pubmed-meshheading:1510695-Rats,
pubmed-meshheading:1510695-Rats, Inbred Strains
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pubmed:year |
1992
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pubmed:articleTitle |
Effects of cysteine and acetaminophen on the syntheses of glutathione and adenosine 3'-phosphate 5'-phosphosulfate in isolated rat hepatocytes.
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pubmed:affiliation |
Department of Medicine A, Rigshospitalet, Copenhagen, Denmark.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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