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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: 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.
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    
*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.
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