Linked Life Data

11032766

Source:http://linkedlifedata.com/resource/pubmed/id/11032766

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-11-9
pubmed:abstractText
CYP2E1 has been reported to have an essential role in alcohol-mediated increases in hepatic steatosis and acetaminophen hepatotoxicity. We found that pretreatment of Cyp2e1(-/-) mice with ethanol plus isopentanol, the predominant alcohols in alcoholic beverages, for 7 days resulted in micro- and macrovesicular steatosis in the livers of all mice, as well as a dramatic increase in acetaminophen hepatotoxicity. In Cyp2e1(-/-) mice administered up to 600 mg acetaminophen/kg alone and euthanized 7 h later, there was no increase in serum levels of ALT. In Cyp2e1(-/-) mice pretreated with ethanol and isopentanol, subsequent exposure to 400 or 600 mg acetaminophen/kg resulted in centrilobular necrosis in all mice with maximal elevation in serum levels of ALT. Acetaminophen-mediated liver damage was similar in males and females. Hepatic microsomal levels of APAP activation in untreated females were similar to those in males treated with the alcohols. However, the females, like the males, required pretreatment with the alcohols in order to increase APAP hepatotoxicity. These findings suggest that, in the Cyp2e1(-/-) mice, the alcohol-mediated increase in acetaminophen hepatotoxicity involves the contribution of other factors, in addition to induction of CYP(s) that activate acetaminophen. Alternatively, CYP-mediated activation of acetaminophen measured in vitro may not reflect the actual activity in vivo. Our findings that a 7-day treatment with ethanol and isopentanol causes extensive hepatic steatosis and increases acetaminophen hepatotoxicity in Cyp2e(-/-) mice indicate that CYP2E1 is not essential for either response.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0041-008X
pubmed:author
pubmed:copyrightInfo
Copyright 2000 Academic Press.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
168
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
114-22
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11032766-Acetaminophen, pubmed-meshheading:11032766-Analgesics, Non-Narcotic, pubmed-meshheading:11032766-Animals, pubmed-meshheading:11032766-Benzoquinones, pubmed-meshheading:11032766-Biotransformation, pubmed-meshheading:11032766-Cytochrome P-450 CYP2E1, pubmed-meshheading:11032766-Drug Synergism, pubmed-meshheading:11032766-Drug-Induced Liver Injury, pubmed-meshheading:11032766-Ethanol, pubmed-meshheading:11032766-Fatty Liver, Alcoholic, pubmed-meshheading:11032766-Female, pubmed-meshheading:11032766-Imines, pubmed-meshheading:11032766-Liver, pubmed-meshheading:11032766-Liver Diseases, pubmed-meshheading:11032766-Male, pubmed-meshheading:11032766-Mice, pubmed-meshheading:11032766-Mice, Inbred C57BL, pubmed-meshheading:11032766-Pentanols, pubmed-meshheading:11032766-Sex Factors
pubmed:year
2000
pubmed:articleTitle
Short-term treatment with alcohols causes hepatic steatosis and enhances acetaminophen hepatotoxicity in Cyp2e1(-/-) mice.
pubmed:affiliation
Veterans Administration Medical Center, White River Junction, Vermont, 05009, USA. JSINC@dartmouth.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.