Next Article in Journal
Brusatol Enhances the Radiosensitivity of A549 Cells by Promoting ROS Production and Enhancing DNA Damage
Next Article in Special Issue
Niemann-Pick Type C2 Protein Mediates Hepatic Stellate Cells Activation by Regulating Free Cholesterol Accumulation
Previous Article in Journal
Chitosan Effects on Plant Systems
Previous Article in Special Issue
Hepatitis B Virus X Protein and Hepatocarcinogenesis
Article Menu
Issue 7 (July) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2016, 17(7), 995; doi:10.3390/ijms17070995

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

1,2,†
,
1,†
,
3
,
1
,
1
,
1,* and 1,*
1
Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China
2
Department of Anesthesiology, The First Affiliated Hospital, University of South China, Hengyang 421001, China
3
Department of Anesthesiology, Fujian Provincial Hospital, Fuzhou 350000, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Johannes Haybaeck
Received: 14 May 2016 / Revised: 14 June 2016 / Accepted: 16 June 2016 / Published: 23 June 2016
(This article belongs to the Collection Molecular Mechanisms of Human Liver Diseases)
View Full-Text   |   Download PDF [4112 KB, uploaded 23 June 2016]   |  

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. View Full-Text
Keywords: dexmedetomidine; ischemia-reperfusion injury; liver transplantation; TLR4/NF-κB; α2A-adrenoceptor subtype dexmedetomidine; ischemia-reperfusion injury; liver transplantation; TLR4/NF-κB; α2A-adrenoceptor subtype
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Wang, Y.; Wu, S.; Yu, X.; Zhou, S.; Ge, M.; Chi, X.; Cai, J. 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. Int. J. Mol. Sci. 2016, 17, 995.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top