|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
5
|
|
pubmed:dateCreated |
2003-10-16
|
|
pubmed:abstractText |
Tumor necrosis factor (TNF)-alpha is a macrophage-derived proinflammatory cytokine implicated in hepatotoxicity. In the present studies, p55 TNF receptor 1 (TNFR1) -/- mice were used to assess the role of TNF-alpha in acetaminophen-induced antioxidant defense. Treatment of wild-type (WT) mice with acetaminophen (300 mg/kg) resulted in centrilobular hepatic necrosis and increased serum alanine transaminases. This was correlated with a rapid depletion of hepatic glutathione (GSH). Whereas in WT mice GSH levels returned to control after 6-12 h, in TNFR1-/- mice recovery was delayed for 48 h. Delayed induction of heme oxygenase-1 and reduced expression of CuZn superoxide dismutase were also observed in TNFR1-/- compared with WT mice. This was associated with exaggerated hepatotoxicity. In WT mice, acetaminophen caused a time-dependent increase in activator protein-1 nuclear binding activity and in c-Jun expression. This response was significantly attenuated in TNFR1-/- mice. Constitutive NF-kappaB binding activity was detectable in livers of both WT and TNFR1-/- mice. A transient decrease in this activity was observed 3 h after acetaminophen in WT mice, followed by an increase that was maximal after 6-12 h. In contrast, in TNFR1-/- mice, acetaminophen-induced decreases in NF-kappaB activity were prolonged and did not return to control levels for 24 h. These data indicate that TNF-alpha signaling through TNFR1 plays an important role in regulating the expression of antioxidants in this model. Reduced generation of antioxidants may contribute to the increased sensitivity of TNFR1-/- mice to acetaminophen.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acetaminophen,
http://linkedlifedata.com/resource/pubmed/chemical/Alanine Transaminase,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Heme Oxygenase (Decyclizing),
http://linkedlifedata.com/resource/pubmed/chemical/Heme Oxygenase-1,
http://linkedlifedata.com/resource/pubmed/chemical/Hmox1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Nov
|
|
pubmed:issn |
0193-1857
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
285
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
G959-66
|
|
pubmed:dateRevised |
2007-11-14
|
|
pubmed:meshHeading |
pubmed-meshheading:12842828-Acetaminophen,
pubmed-meshheading:12842828-Alanine Transaminase,
pubmed-meshheading:12842828-Animals,
pubmed-meshheading:12842828-Antigens, CD,
pubmed-meshheading:12842828-Antioxidants,
pubmed-meshheading:12842828-Enzyme Induction,
pubmed-meshheading:12842828-Glutathione,
pubmed-meshheading:12842828-Heme Oxygenase (Decyclizing),
pubmed-meshheading:12842828-Heme Oxygenase-1,
pubmed-meshheading:12842828-Liver,
pubmed-meshheading:12842828-Male,
pubmed-meshheading:12842828-Membrane Proteins,
pubmed-meshheading:12842828-Mice,
pubmed-meshheading:12842828-Mice, Inbred C57BL,
pubmed-meshheading:12842828-Mice, Knockout,
pubmed-meshheading:12842828-NF-kappa B,
pubmed-meshheading:12842828-Necrosis,
pubmed-meshheading:12842828-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:12842828-Receptors, Tumor Necrosis Factor, Type I,
pubmed-meshheading:12842828-Superoxide Dismutase,
pubmed-meshheading:12842828-Transcription Factor AP-1
|
|
pubmed:year |
2003
|
|
pubmed:articleTitle |
Role of p55 tumor necrosis factor receptor 1 in acetaminophen-induced antioxidant defense.
|
|
pubmed:affiliation |
Dept. of Pharmacology and Toxicology, Rutgers Univ., 170 Frelinghuysen Rd., Piscataway, NJ 08854-8020, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|
