title: 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.
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: Department of Anesthesiology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.
authors: Fujing
authors: F
authors: Li
authors: Zhixia
authors: Z
authors: Chen
authors: Qiuhui
authors: Q
authors: Pan
authors: Shukun
authors: S
authors: Fu
authors: Fuqing
authors: F
authors: Lin
authors: Hao
authors: H
authors: Ren
authors: Huanxing
authors: H
authors: Han
authors: Timothy R
authors: TR
authors: Billiar
authors: Fenyong
authors: F
authors: Sun
authors: Quan
authors: Q
authors: Li
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors*; D008099:Liver / Q000098:blood supply; D008107:Liver Diseases / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D001549:Benzamides; D001643:Bridged Bicyclo Compounds; C579166:Chrna7 protein, mouse; D016207:Cytokines; D024243:HMGB1 Protein; D016328:NF-kappa B; D018722:Nicotinic Agonists; C498513:PNU-282987; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor