title: Dexmedetomidine premedication attenuates concanavalin A-induced hepatitis in mice.
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.
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, China.
authors.forename: Haibin
authors.initials: H
authors.lastname: Wang
authors.forename: Baoji
authors.initials: B
authors.lastname: Hu
authors.forename: Yun
authors.initials: Y
authors.lastname: Zou
authors.forename: Lulong
authors.initials: L
authors.lastname: Bo
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Jinbao
authors.initials: J
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D056487:Chemical and Drug Induced Liver Injury, Chronic / Q000188:drug therapy* / Q000276:immunology*; D054357:Chemokine CXCL10 / Q000378:metabolism; D003208:Concanavalin A; D016207:Cytokines / Q000097:blood; D020927:Dexmedetomidine / Q000494:pharmacology* / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood; D008099:Liver / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D054357:Chemokine CXCL10; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D003208:Concanavalin A; D020927:Dexmedetomidine