Linked Life Data

19295477

Source:http://linkedlifedata.com/resource/pubmed/id/19295477

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-10-22
pubmed:abstractText
We have recently found that suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, improves survival in a lethal model of hemorrhagic shock in rats. The purpose of the present study was to determine whether SAHA treatment would prevent LPS-induced septic shock and improve the survival in a murine model. C57BL/6J mice were randomly divided into two groups. Experimental mice were given intraperitoneal SAHA (50 mg/kg) in vehicle dimethyl sulfoxide fluid (n = 10). The control mice (n = 10) received vehicle dimethyl sulfoxide only. They were injected with LPS (20 mg/kg, i.p.) 2 h later, and the animals from the treatment group were given a second dose of SAHA. Survival was monitored during the next 7 days. In a parallel study, mice treated with or without SAHA were subjected to LPS insult while normal (sham) mice serviced as controls. 1) Lungs were harvested at 3 and 48 h for analysis of gene expression and pathologic changes, respectively; 2) spleens were isolated for analysis of neutrophilic cell population. In addition, RAW264.7 mouse macrophages were cultured to assess the effects of SAHA on LPS-induced inflammation in vitro. All mice in the control group that were subjected to LPS challenge died in less than 48 h. However, SAHA-treated animals displayed a significantly higher 1-week survival rate (87.5%) compared with the control group (0%). Moreover, LPS insult decreased the acetylation of histone proteins (H2A, H2B, and H3), elevated the levels of TNF-alpha in vivo (circulation) and in vitro (culture medium), increased the neutrophilic cell population in the spleen, enhanced the expression of TNF-alpha and IL-1beta genes in lung tissue, and augmented the pulmonary neutrophil infiltration. In contrast, SAHA treatment markedly attenuated all of these LPS-induced alterations. We report for the first time that administration of SAHA (50 mg/kg) significantly attenuates a variety of inflammatory markers and improves long-term survival after a lethal LPS insult.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1540-0514
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
517-23
pubmed:dateRevised
2011-2-1
pubmed:meshHeading
pubmed-meshheading:19295477-Acetylation, pubmed-meshheading:19295477-Acute Lung Injury, pubmed-meshheading:19295477-Animals, pubmed-meshheading:19295477-Blotting, Western, pubmed-meshheading:19295477-Cell Line, Tumor, pubmed-meshheading:19295477-Flow Cytometry, pubmed-meshheading:19295477-Histone Deacetylase Inhibitors, pubmed-meshheading:19295477-Histones, pubmed-meshheading:19295477-Hydroxamic Acids, pubmed-meshheading:19295477-Interleukin-1beta, pubmed-meshheading:19295477-Lipopolysaccharides, pubmed-meshheading:19295477-Male, pubmed-meshheading:19295477-Mice, pubmed-meshheading:19295477-Mice, Inbred C57BL, pubmed-meshheading:19295477-Peroxidase, pubmed-meshheading:19295477-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19295477-Shock, Septic, pubmed-meshheading:19295477-Tumor Necrosis Factor-alpha
pubmed:year
2009
pubmed:articleTitle
Protective effect of suberoylanilide hydroxamic acid against LPS-induced septic shock in rodents.
pubmed:affiliation
Department of Surgery, Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02114, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't