Linked Life Data

8812234

Source:http://linkedlifedata.com/resource/pubmed/id/8812234

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1996-12-20
pubmed:abstractText
Acetaminophen is an analgesic and antipyretic which causes liver toxicity in humans and experimental animals with overdose. Acetaminophen (APAP) covalent binding to a cytosolic protein of approximately 58 kDa (58-ABP) has been associated with target organ toxicity. Since hepatic content of 58-ABP varies, studies were conducted to determine if this influences APAP binding to other target proteins. In the liver, the amount of 58-ABP varied with individual male CD-1 mice, but in kidneys of the same mice there was no such variability in 58-ABP content. All male A/J mice tested had comparatively little detectable 58-ABP in liver cytosol. Similarly, female CD-1 mice had low 58-ABP content compared to males; however, administration of testosterone propionate to females significantly increased 58-ABP content in liver cytosol. At 4 hr after challenge of mice from the above-described groups with 600 mg APAP/kg, cytosolic covalent binding to proteins was determined by Western blot analysis with anti-APAP antibody. The Western blots were then stripped of antibody and blocking agents and reprobed with antibody prepared against purified 58-ABP (anti-58-ABP). In the liver, the level of APAP bound to the 58-ABP target corresponded with 58-ABP content. In cases where 58-ABP was poorly expressed, APAP adducts to other protein targets were more prominently detected. In the kidneys of the male CD-1 mice 58-ABP arylation by APAP varied little among animals, reflecting the relatively consistent levels of renal 58-ABP. These data suggest that binding to the 58-ABP may spare other potential targets of APAP electrophile attach and support a role of the 58-ABP as a preferred target of APAP electrophile in cytosol.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0272-0590
pubmed:author
pubmed:issnType
Print
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
79-86
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Evidence suggesting the 58-kDa acetaminophen binding protein is a preferential target for acetaminophen electrophile.
pubmed:affiliation
Department of Pharmaceutical Sciences, University of Connecticut, Storrs 06269-2092, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't