Linked Life Data

8209379

Source:http://linkedlifedata.com/resource/pubmed/id/8209379

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1994-7-12
pubmed:abstractText
Acetaminophen (APAP) administration (600 mg/kg, ip) to 18-hr-fasted, 3-month-old male CD-1 mice results in necrosis of the renal convoluted proximal tubules. To selectively inhibit APAP activation in the kidney but not in the liver, 10-week-old male CD-1 mice were castrated under ether anesthesia and allowed to recover for a minimum of 2 weeks before use. Microsomal activation of APAP in vitro was monitored by trapping the APAP-derived electrophile as an N-acetylcysteine conjugate. Production of the conjugate was significantly decreased in renal microsomes from castrated mice. By contrast, hepatic microsomal production of the APAP conjugate was not changed by castration. Castration also did not alter APAP covalent binding in liver or APAP hepatotoxicity. Also, the overall metabolism of APAP was not altered by castration, as there were no significant differences in the 24-hr excretion of APAP urinary metabolites between castrated and sham-operated mice. However, castration did significantly protect mice against APAP nephrotoxicity, as evidenced by decreases in plasma urea nitrogen levels and in the severity of histopathologic damage assessed 12 hr after APAP. Castration also reduced the level of selective covalent binding of APAP metabolites to renal proteins as detected on Western blots with affinity-purified anti-APAP antibodies. These findings suggest that, for the mouse, intrarenal biotransformation of APAP to a reactive electrophile significantly contributes to the APAP covalent binding within the kidneys and the subsequent nephrotoxicity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0041-008X
pubmed:author
pubmed:issnType
Print
pubmed:volume
126
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
267-75
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Acetaminophen nephrotoxicity in CD-1 mice. I. Evidence of a role for in situ activation in selective covalent binding and toxicity.
pubmed:affiliation
Department of Pathobiology, University of Connecticut, Storrs 06029-2092.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't