| The Protective Effect of PNU-282987, a Selective α7 Nicotinic Acetylcholine Receptor Agonist, on the Hepatic Ischemia-Reperfusion Injury Is Associated With the Inhibition of High-Mobility Group Box 1 Protein Expression and Nuclear Factor κB Activation in Mice. | |
| | |
MedLine Citation:
|
PMID: 23324890 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
ABSTRACT: Hepatic ischemia-reperfusion (I/R) injury contributes to hepatic dysfunction and failure after liver transplantation, major hepatic resection, trauma, and hypovolemic shock. Therefore, reducing I/R injury is an important goal to improve the outcome of these procedures. Recently, high-mobility group box 1 protein (HMGB1) has been identified as a pathogenic mediator in several inflammatory diseases, including hepatic I/R. PNU-282987, a selective α7 nicotinic acetylcholine receptor agonist, prevents nuclear factor κB (NF-κB) activation and thereby inhibits cytokine secretion through a specific cholinergic anti-inflammatory pathway. Our study was designed to evaluate whether PNU-282987 would inhibit HMGB1 expression and prevent I/R-induced liver damage. C57BL/6 mice were randomly divided into 3 groups as follows: sham group, vehicle plus I/R group, and PNU-282987 plus I/R group. Mice were subjected to 70% partial hepatic I/R for 60 min and pretreated with either vehicle or with PNU-282987, and blood and hepatic tissue samples were collected at 3, 6, and 12 h following reperfusion. The results showed that pretreatment with PNU-282987 decreased serum transaminase levels and ameliorated liver injury after hepatic I/R. Moreover, pretreatment with PNU-282987 suppressed NF-κB activation, cytokine production (tumor necrosis factor α, interleukin 1β), and HMGB1 expression in liver after hepatic I/R. These observations suggest that PNU-282987 protects the liver from I/R injury possibly by inhibiting HMGB1 expression, suppressing cytokine production, and preventing NF-κB activation in mice. |
| | |
Authors:
|
Fujing Li; Zhixia Chen; Qiuhui Pan; Shukun Fu; Fuqing Lin; Hao Ren; Huanxing Han; Timothy R Billiar; Fenyong Sun; Quan Li |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Shock (Augusta, Ga.) Volume: 39 ISSN: 1540-0514 ISO Abbreviation: Shock Publication Date: 2013 Feb |
Date Detail:
|
Created Date: 2013-01-17 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9421564 Medline TA: Shock Country: United States |
Other Details:
|
Languages: eng Pagination: 197-203 Citation Subset: IM |
Affiliation:
|
*Department of Anesthesiology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai; †Nanchang University, School of Medicine, Nanchang; and ‡Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China; §Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania; and ∥Translational Medical Center, Changzheng Hospital, SMMU, Shanghai, China. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Activation of the heat shock response attenuates the interleukin 1?-mediated inhibition of the amilo...
Next Document: Fluid resuscitation of uncontrolled hemorrhage using a hemoglobin-based oxygen carrier: effect of t...