| pubmed-article:19295477 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19295477 | lifeskim:mentions | umls-concept:C0035804 | lld:lifeskim |
| pubmed-article:19295477 | lifeskim:mentions | umls-concept:C0036983 | lld:lifeskim |
| pubmed-article:19295477 | lifeskim:mentions | umls-concept:C1280500 | lld:lifeskim |
| pubmed-article:19295477 | lifeskim:mentions | umls-concept:C0672708 | lld:lifeskim |
| pubmed-article:19295477 | pubmed:issue | 5 | lld:pubmed |
| pubmed-article:19295477 | pubmed:dateCreated | 2009-10-22 | lld:pubmed |
| pubmed-article:19295477 | 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. | lld:pubmed |
| pubmed-article:19295477 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19295477 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19295477 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19295477 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:19295477 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19295477 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19295477 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19295477 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19295477 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19295477 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19295477 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19295477 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19295477 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19295477 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:19295477 | pubmed:issn | 1540-0514 | lld:pubmed |
| pubmed-article:19295477 | pubmed:author | pubmed-author:FukudomeEugen... | lld:pubmed |
| pubmed-article:19295477 | pubmed:author | pubmed-author:AlamHasan BHB | lld:pubmed |
| pubmed-article:19295477 | pubmed:author | pubmed-author:VelmahosGeorg... | lld:pubmed |
| pubmed-article:19295477 | pubmed:author | pubmed-author:ZhaoHangH | lld:pubmed |
| pubmed-article:19295477 | pubmed:author | pubmed-author:ZhangXiaoboX | lld:pubmed |
| pubmed-article:19295477 | pubmed:author | pubmed-author:LiYongqingY | lld:pubmed |
| pubmed-article:19295477 | pubmed:author | pubmed-author:HalesCharles... | lld:pubmed |
| pubmed-article:19295477 | pubmed:author | pubmed-author:SailhamerEliz... | lld:pubmed |
| pubmed-article:19295477 | pubmed:author | pubmed-author:LiuBaolingB | lld:pubmed |
| pubmed-article:19295477 | pubmed:author | pubmed-author:deMoyaMarcM | lld:pubmed |
| pubmed-article:19295477 | pubmed:author | pubmed-author:KheirbekTareq... | lld:pubmed |
| pubmed-article:19295477 | pubmed:author | pubmed-author:FinkelsteinRo... | lld:pubmed |
| pubmed-article:19295477 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:19295477 | pubmed:volume | 32 | lld:pubmed |
| pubmed-article:19295477 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19295477 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19295477 | pubmed:pagination | 517-23 | lld:pubmed |
| pubmed-article:19295477 | pubmed:dateRevised | 2011-2-1 | lld:pubmed |
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| pubmed-article:19295477 | pubmed:meshHeading | pubmed-meshheading:19295477... | lld:pubmed |
| pubmed-article:19295477 | pubmed:year | 2009 | lld:pubmed |
| pubmed-article:19295477 | pubmed:articleTitle | Protective effect of suberoylanilide hydroxamic acid against LPS-induced septic shock in rodents. | lld:pubmed |
| pubmed-article:19295477 | pubmed:affiliation | Department of Surgery, Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02114, USA. | lld:pubmed |
| pubmed-article:19295477 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:19295477 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:19295477 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:19295477 | lld:pubmed |
