Dexmedetomidine alleviated lipopolysaccharide/D-galactosamine-induced acute liver injury in mice

Abstract

Dexmedetomidine (DEX), a highly selective α2-adrenergic receptor (α2-AR) agonist, is widely used as sedative in clinical. Its potential anti-inflammatory properties have been found in recent studies. The current study has investigated the profound effects of DEX on acute liver injury in mice. The mice were intraperitoneally injected lipopolysaccharide (LPS) and D-galactosamine (D-Gal) to induce acute liver injury, and vehicle or DEX were treated 30 min before or 2 h after LPS/D-Gal exposure. The results showed that pre-treatment with DEX inhibited the raising of plasma aminotransferases, reduced the damage of liver tissue, and improved the survival rate in mice exposed to LPS/D-Gal. Pre-treatment with DEX also inhibited the release of TNF-α and suppressed the phosphorylation of c-jun-N-terminal kinase (JNK) in mice exposed to LPS/D-Gal. In addition, pre-treatment with DEX down-regulated the expression of cleavage of caspase-3, decreased the activities of caspase-3, caspase-8, caspase-9, and consequently, reduced hepatocyte apoptosis. Interestingly, post-treatment with DEX also resulted in beneficial outcomes. The current study indicates that administration of DEX might provide protective benefits in inflammatory liver disease.

Keywords: Acute liver injury; Apoptosis; Dexmedetomidine; Inflammation; c-Jun-N-terminal kinase.