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.

Dexmedetomidine activates the PI3K/Akt pathway to inhibit hepatocyte apoptosis in rats with obstructive jaundice

“…The results of the present study demonstrated that Dex could not only significantly improve the pathological morphology of liver tissues and the changes of hepatic function parameters ALT, AST and TBIL, but also inhibit the expression levels of serum inflammatory cytokines IL-6 and TNF-α in rats with OJ. The present findings indicated that Dex had a protective effect on hepatic injury caused by OJ through reducing the levels of serum inflammatory cytokines IL-6 and TNF-α, which is in agreement with the studies of Venn et al (23) and Wang et al (24).…”

Critical roles of conventional dendritic cells in autoimmune hepatitis via autophagy regulation

“…The EAH model was established at 12 h after an injection of ConA with a dose of 20 mg/kg through the tail vein, which was based on our previous study and other reported articles [11][12][13][14] . To evaluate the EAH model, the mice were divided into two groups: (1) Mice were given a single intravenous injection of normal saline as a vehicle control.…”

Hepatoprotective Effect of Dexmedetomidine Against Radioiodine Toxicity in Rats: Evaluation of Oxidative Status and Histopathologic Changes

“…The positive effects of DEX are emanated from the anti-inflammatory, antioxidant, and anti-apoptotic properties of this compound. [6][7][8][9][10] Moreover, preclinical studies on DEX have indicated that DEX could be a good option for treating T cell-mediated liver injury, 11 and it has beneficial effects on the liver in experimental liver injury models including ischemia-reperfusion and obstructive jaundice. 12,13 It was concluded that these effects of DEX might also be due to its antioxidant and anti-inflammatory activities.…”