Alpha-ketoglutarate alleviates cholestatic liver injury in mice

Abstract

Objective To investigate the alleviating effects of alpha-ketoglutarate (AKG) on bile duct ligation (BDL)-induced cholestatic liver injury in mice and its possible mechanism. Methods Thirty-two C57BL/6 male mice were randomly assigned to 4 groups (n=8): sham operation group (Sham), sham operation+AKG group (Sham+AKG), BDL group and BDL+AKG group. Liver and blood samples were collected from all groups in 7 d after operation, and the serum levels of ALT, AST, TBIL, TBA and ALP were measured. HE staining and immunohistochemistry were used to detect the severity of liver injury and the expression of F4/80 and myeloperoxidase (MPO) in each group, respectively. qRT-PCR was adopted to determine the mRNA expression of pro-inflammatory cytokines. Hepatocyte apoptosis was evaluated by TUNEL assay. Results As compared with the BDL group, the BDL+AKG group showed significantly lower concentrations of ALT, AST, TBIL, TBA and ALP (P < 0.05), obviously relieved liver histologic injury (P < 0.05), reduced expression levels of F4/80 and MPO as well as pro-inflammatory cytokines (P < 0.05), and decreased number of TUNEL positive hepatocytes (P < 0.05). Conclusion AKG alleviates hepatic injury in BDL-induced cholestasis model mice, and its mechanism is possibly related to the inhibition of inflammatory response and hepatic cell apoptosis.

Keywords

• alpha-ketoglutarate
• cholestatic liver injury
• inflammatory response
• apoptosis
• mice