Dexmedetomidine (DEX) protects against hepatic ischemia/reperfusion (I/R) injury by suppressing inflammation and oxidative stress in NLRC5 deficient mice

Biochem Biophys Res Commun. 2017 Nov 18;493(2):1143-1150. doi: 10.1016/j.bbrc.2017.08.017. Epub 2017 Aug 4.


Hepatic ischemia/reperfusion (I/R) injury could arise as a complication of liver surgery and transplantation. No specific therapeutic strategies are available to attenuate I/R injury. NOD-, LRR-and CARD-containing 5 (NLRC5), a member of the NOD-like protein family, has been suggested to negatively regulate nuclear factor kappa B (NF-κB) through interacting with IKKα and blocking their phosphorylation. Dexmedetomidine (DEX) has been shown to attenuate liver injury. In the current study, we investigated the pre-treatment of DEX on hepatic I/R injury in wild type (WT) and NLRC5 knockout (NLRC5-/-) mice. Our results indicated that NLRC5-/- showed significantly stronger histologic damage, inflammatory response, oxidative stress and apoptosis after I/R compared to the WT group of mice, indicating the protective role of NLRC5 against liver I/R injury. Importantly, I/R-induced increase of NLRC5 was reduced by DEX pre-treatment. After hepatic I/R injury, WT and NLRC5-/- mice pre-treated with DEX exhibited attenuated histological disruption, and reduced pro-inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β and inducible nitric oxide synthase (iNOS), which was associated with the inactivated NF-κB pathway. Moreover, suppression of oxidative stress and apoptosis was observed in DEX-treated mice with I/R injury, probably through enhancing nuclear factor erythroid 2-related factor 2 (Nrf2), reducing mitogen-activated protein kinases (MAPKs) and Caspase-3/poly (ADP-ribose) polymerase (PARP) pathways. In vitro, the results were further confirmed in WT and NLRC5-/- hepatocytes pre-treated with or without DEX. Together, the findings illustrated that lack of NLRC5 resulted in severer liver I/R injury, which could be alleviated by DEX pre-treatment.

Keywords: Dexmedetomidine; Hepatic ischemia/reperfusion (I/R) injury; Inflammation; NLRC5; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / therapeutic use
  • Apoptosis / drug effects
  • Cells, Cultured
  • Dexmedetomidine / therapeutic use*
  • Gene Deletion
  • Hypnotics and Sedatives / therapeutic use*
  • Inflammation / drug therapy*
  • Inflammation / genetics
  • Inflammation / pathology
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oxidative Stress / drug effects*
  • Protective Agents / therapeutic use*
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / genetics
  • Reperfusion Injury / pathology


  • Anti-Inflammatory Agents
  • Antioxidants
  • Hypnotics and Sedatives
  • Intracellular Signaling Peptides and Proteins
  • NLRC5 protein, mouse
  • Protective Agents
  • Dexmedetomidine