Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-8-13
pubmed:abstractText
Insulin-like growth factor (IGF) 1 has protective effects in liver failure. However, the effect of IGF-1 on inflammatory mediators such as proinflammatory cytokines and NO remains to be clarified. We hypothesized that IGF-1 inhibited the induction of these cytokines and iNOS, resulting in beneficial effect in the liver. Rats were treated with D-galactosamine (400 mg kg(-1)) and LPS (16 microg kg(-1)) (GalN/LPS) to induce acute liver failure. Insulin-like growth factor 1 (3.2 mg kg(-1)) was administered subcutaneously before GalN/LPS injection. Insulin-like growth factor 1 increased the survival rate in GalN/LPS-treated rats and prevented the increases of transaminases and total bilirubin in serum. Histopathological analysis revealed that IGF-1 decreased the incidence of hepatic apoptosis and neutrophil infiltration. Insulin-like growth factor 1 inhibited increases in TNF-alpha, IL-1 beta, and cytokine-induced neutrophil chemoattractant 1 caused by GalN/LPS in serum and liver and enhanced serum IL-10. Insulin-like growth factor 1 reduced the induction of iNOS mRNA and its protein in GalN/LPS-treated liver and resulted in a decrease in NO production. However, IGF-1 had no effect on the activation of nuclear factor-kappa B. Analysis of iNOS antisense-transcript revealed that IGF-1 accelerated the degradation of iNOS mRNA, rather than the inhibition of its synthesis. Insulin-like growth factor 1 may inhibit the induction of proinflammatory cytokines and iNOS through an nuclear factor-kappa B-independent pathway and have a novel therapeutic potential in the prevention of liver injury.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1073-2322
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
740-7
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Insulin-like growth factor 1 prevents liver injury through the inhibition of TNF-alpha and iNOS induction in D-galactosamine and LPS-treated rats.
pubmed:affiliation
The Department of Surgery, Kansai Medical University, Moriguchi, Osaka, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't