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pubmed-article:10438658pubmed:abstractTextTumor 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.lld:pubmed
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pubmed-article:10438658pubmed:authorpubmed-author:KahnTTlld:pubmed
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pubmed-article:10438658pubmed:copyrightInfoCopyright 1999 Academic Press.lld:pubmed
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pubmed-article:10438658pubmed:pagination253-60lld:pubmed
pubmed-article:10438658pubmed:dateRevised2006-11-15lld:pubmed
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pubmed-article:10438658pubmed:articleTitleInfluence of tumor necrosis factor-alpha and silibin on the cytotoxic action of alpha-amanitin in rat hepatocyte culture.lld:pubmed
pubmed-article:10438658pubmed:affiliationInstitute of Toxicology, University of Düsseldorf, Düsseldorf, Germany.lld:pubmed
pubmed-article:10438658pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:10438658pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed