title: Dexmedetomidine Protects Rat Liver against Ischemia-Reperfusion Injury Partly by the α2A-Adrenoceptor Subtype and the Mechanism Is Associated with the TLR4/NF-κB Pathway.
abstract: Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling plays a dominant role in the pathogenesis of liver ischemia-reperfusion (IR) injury. Dexmedetomidine (Dex) protects the liver against IR injury via α₂-adrenoceptor activation, but the contribution of TLR4 signaling remains unknown. The authors aimed to examine whether pretreatment with Dex produces hepatic protection and investigate the influence of Dex on TLR4/NF-κB signaling. Dex was given via intraperitoneal injection 30 min prior to orthotopic autologous liver transplantation (OALT) in rats, and three α₂-adrenoceptor antagonists including atipamezole (a nonselective α₂ receptor blocker), ARC-239 (a specific α2B/C blocker) and BRL-44408 (a specific α2A blocker) were injected intraperitoneally 10 min before Dex administration. Histopathologic evaluation of the liver and the measurement of serum alanine aminotransferase activity, TLR4/NF-κB expression in the liver, and pro-inflammatory factors (serum tumor necrosis factor-α, interleukin-1β and hepatic myeloperoxidase) concentrations were performed 8 h after OALT. Dex ameliorated liver injury after OALT probably by suppressing the TLR4/NF-κB pathway and decreasing inflammatory mediator levels. The protective effects of Dex were reversed by atipamezole and BRL-44408, but not by ARC-239, suggesting that these effects were mediated in part by the α2A subtype. In conclusion, Dex attenuates liver injury partly via the α2A-adrenoceptor subtype, and the mechanism is due to the suppression of the TLR4/NF-κB pathway.
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China. wyheng1202@126.com.|Department of Anesthesiology, The First Affiliated Hospital, University of South China, Hengyang 421001, China. wyheng1202@126.com.
authors.forename: Yiheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China. wsbiosci@sina.com.
authors.forename: Shan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, Fujian Provincial Hospital, Fuzhou 350000, China. yxfanesthesia@hotmail.com.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China. doctorzsl@sina.com.
authors.forename: Shaoli
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China. gmsunyatsen@sina.com.
authors.forename: Mian
authors.initials: M
authors.lastname: Ge
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China. chixinjin@yeah.net.
authors.forename: Xinjin
authors.initials: X
authors.lastname: Chi
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China. biomedcaijun@hotmail.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D053583:Interleukin-1beta / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D053583:Interleukin-1beta; D016328:NF-kappa B; D018341:Receptors, Adrenergic, alpha-2; D051197:Toll-Like Receptor 4; D020927:Dexmedetomidine; D009195:Peroxidase
keywords: TLR4/NF-κB; dexmedetomidine; ischemia-reperfusion injury; liver transplantation; α2A-adrenoceptor subtype