Source:http://linkedlifedata.com/resource/pubmed/id/10438658
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1999-8-26
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pubmed:abstractText |
Tumor necrosis factor-alpha is assumed to play a role in toxic liver damage. We examined whether exogenous tumor necrosis factor-alpha must be present for alpha-amanitin cytotoxicity in rat hepatocyte culture. alpha-Amanitin at a concentration of 0.1 microM, which is close to that found in intoxicated patients, inhibits RNA and protein synthesis within 12 h but cytotoxicity only occurs after a latency period and is pronounced at 36 h after the start of treatment. Tumor necrosis factor-alpha is not indispensable for the development of cytotoxicity but aggravates it and leads to a time shift towards earlier times. Lipid peroxidation is low with alpha-amanitin alone even at 36 h but markedly increased by cotreatment with tumor necrosis factor-alpha. The antioxidant silibin prevents the effect of tumor necrosis factor-alpha, indicating an involvement of reactive oxygen species. alpha-Amanitin alone does not increase but dose-dependently inhibits the expression of the antioxidant enzyme manganous superoxide dismutase and decreases the inducing effect of TNF-alpha on the expression of this enzyme. The gene expression of endogenous tumor necrosis factor-alpha in the hepatocytes is not increased but rather inhibited by alpha-amanitin treatment. The results suggest that alpha-amanitin causes delayed cytotoxicity following rapid inhibition of RNA and protein synthesis and that tumor necrosis factor-alpha shortens the latency period and aggravates the cytotoxicity by a mechanism which may involve reactive oxygen species.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amanitins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/Silymarin,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0041-008X
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 1999 Academic Press.
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
158
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
253-60
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:10438658-Amanitins,
pubmed-meshheading:10438658-Animals,
pubmed-meshheading:10438658-Blotting, Northern,
pubmed-meshheading:10438658-Cell Survival,
pubmed-meshheading:10438658-Cells, Cultured,
pubmed-meshheading:10438658-Liver,
pubmed-meshheading:10438658-Male,
pubmed-meshheading:10438658-Protein Biosynthesis,
pubmed-meshheading:10438658-RNA,
pubmed-meshheading:10438658-Rats,
pubmed-meshheading:10438658-Rats, Wistar,
pubmed-meshheading:10438658-Silymarin,
pubmed-meshheading:10438658-Superoxide Dismutase,
pubmed-meshheading:10438658-Tumor Necrosis Factor-alpha
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pubmed:year |
1999
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pubmed:articleTitle |
Influence of tumor necrosis factor-alpha and silibin on the cytotoxic action of alpha-amanitin in rat hepatocyte culture.
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pubmed:affiliation |
Institute of Toxicology, University of Düsseldorf, Düsseldorf, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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