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Titolo:
Decreased fumonisin hepatotoxicity in mice with a targeted deletion of tumor necrosis factor receptor 1
Autore:
Sharma, RP; Bhandari, N; He, QR; Riley, RT; Voss, KA;
Indirizzi:
Univ Georgia, Coll Vet Med, Dept Physiol & Pharmacol, Athens, GA 30602 USAUniv Georgia Athens GA USA 30602 hysiol & Pharmacol, Athens, GA 30602 USA USDA ARS, Toxicol & Mycotoxin Res Unit, Athens, GA 30604 USA USDA ARS Athens GA USA 30604 l & Mycotoxin Res Unit, Athens, GA 30604 USA
Titolo Testata:
TOXICOLOGY
fascicolo: 1-2, volume: 159, anno: 2001,
pagine: 69 - 79
SICI:
0300-483X(20010221)159:1-2<69:DFHIMW>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
FACTOR TNF RECEPTORS; FACTOR-ALPHA; TOXICITY; LACKING; LIVER; P55; INFLAMMATION; APOPTOSIS; CORN; P75;
Keywords:
fumonisin; tumor necrosis factor; tumor necrosis factor receptor; hepatotoxicity; mice; TNF receptor 1 knockout mice;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Sharma, RP Univ Georgia, Coll Vet Med, Dept Physiol & Pharmacol, Athens, GA 30602 USA Univ Georgia Athens GA USA 30602 armacol, Athens, GA 30602 USA
Citazione:
R.P. Sharma et al., "Decreased fumonisin hepatotoxicity in mice with a targeted deletion of tumor necrosis factor receptor 1", TOXICOLOGY, 159(1-2), 2001, pp. 69-79

Abstract

Fumonisin B-1 (FB1), a mycotoxin produced by Fusarium verticillioides and related fungi infests corn and other cereals, and causes a variety of toxiceffects in different mammalian species. Hepatotoxicity is a common toxic response in most species. The cellular responses of FB, involve inhibition of ceramide synthase leading to accumulation of free sphingoid bases and a corresponding induction of tumor necrosis factor alpha (TNF alpha). We recently reported that FB, hepatotoxicity was considerably reduced in a mouse strain lacking tumor necrosis factor receptor 2 (TNFR2 or TNFR1b). To furtherinvestigate the relative contribution of the two TNF alpha receptors (TNFR1 and TNFR2 or P55 and P75 receptors) we evaluated the hepatotoxicity of FB, in male C57BL/6J mice (WT) and a corresponding TNFR1 knockout (TNFRKO) strain, genetically modified by a targeted deletion of this receptor. The hepatotoxic effects of five daily injections of 2.25 mg/kg per day of FB, wereobserved in WT but were reduced in TNFRKO, evidenced by the microscopic evaluation of the liver and increased concentrations of circulating alanine aminotransferase and aspartate aminotransferase. FB, induced the expression of TNFa. and similar increases in free sphinganine and sphingosine in livers of both WT and TNFRKO mice. Results indicated that both P55 and P75 receptors are required for FB1-induced hepatotoxicity and TNF alpha plays an important role in such response in mouse liver. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

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Documento generato il 05/04/20 alle ore 09:38:56