1. 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
- Author
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Mian Ge, Xinjin Chi, Shan Wu, Shaoli Zhou, Yiheng Wang, Jun Cai, and Xiaofang Yu
- Subjects
0301 basic medicine ,Male ,medicine.medical_treatment ,Interleukin-1beta ,Liver transplantation ,Pharmacology ,lcsh:Chemistry ,Rats, Sprague-Dawley ,0302 clinical medicine ,Adrenergic alpha-2 Receptor Agonists ,Receptor ,lcsh:QH301-705.5 ,Spectroscopy ,α2A-adrenoceptor subtype ,Liver injury ,biology ,liver transplantation ,NF-kappa B ,Atipamezole ,dexmedetomidine ,General Medicine ,Adrenergic alpha-2 Receptor Antagonists ,Computer Science Applications ,Liver ,030220 oncology & carcinogenesis ,Myeloperoxidase ,Anesthesia ,Reperfusion Injury ,Tumor necrosis factor alpha ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug ,ischemia-reperfusion injury ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Receptors, Adrenergic, alpha-2 ,medicine ,Animals ,Physical and Theoretical Chemistry ,Molecular Biology ,Peroxidase ,business.industry ,Organic Chemistry ,medicine.disease ,Rats ,Toll-Like Receptor 4 ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,biology.protein ,TLR4 ,TLR4/NF-κB ,business ,Reperfusion injury - 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.
- Published
- 2016