Dexmedetomidine premedication attenuates concanavalin A-induced hepatitis in mice

J Toxicol Sci. 2014;39(5):755-64. doi: 10.2131/jts.39.755.

Abstract

Activated T cells selectively induced by concanavalin A (Con A) in liver are subsequent efficient resolution of inflammation. Activated T cells infiltrating in liver combined with pro-inflammatory cytokines are the major causes in Con A-induced liver injury. In our study, C57/BL mice were injected with Con A combined with dexmedetomidine or not. ALT and AST in blood and histopathology of liver were measured. T cell infiltration in liver was examined by flow cytometry and pro-inflammatory cytokines including IL-6, IL-10, TNF-α, and IFN-γ in blood were measured by ELISA. The mRNA level of CXCL10 was detected by RT-PCR and the protein level of NF-κB was measured by Western-blot. We found that dexmedetomidine alleviated Con A-induced liver injury by down-regulating levels of ALT and AST in blood and the severity of histopathology, which reflect the severity of hepatitis induced by Con A. In addition, pro-inflammatory cytokines in blood were attenuated by dexmedetomidine. Dexmedetomidine restrained the phosphorylation of NF-κB IκBα and P-65 dramatically which may participate in the regulation of cytokines secretion. Moreover, CXCL10 mRNA attenuated by dexmedetomidine in liver may result in the lower level of CD4(+) T cells infiltration in liver. These results suggested that dexmedetomidine might be a potential compound in treating T cell-mediated liver injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-2 Receptor Agonists / pharmacology*
  • Adrenergic alpha-2 Receptor Agonists / therapeutic use*
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • Chemical and Drug Induced Liver Injury, Chronic / drug therapy*
  • Chemical and Drug Induced Liver Injury, Chronic / immunology*
  • Chemokine CXCL10 / metabolism
  • Concanavalin A*
  • Cytokines / blood
  • Dexmedetomidine / pharmacology*
  • Dexmedetomidine / therapeutic use*
  • Inflammation Mediators / blood
  • Liver / immunology*
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Phosphorylation / drug effects

Substances

  • Adrenergic alpha-2 Receptor Agonists
  • Chemokine CXCL10
  • Cytokines
  • Inflammation Mediators
  • NF-kappa B
  • Concanavalin A
  • Dexmedetomidine