Abstract: Objective This experiment was conducted to explore the mechanism of protective roles of histone deacetylase (HDAC) inhibitor ACY1215 in inhibition of acute liver failure (ALF). Methods Thirty mice were randomly divided into control, model and ACY1215-intervened groups, with 10 animals in each. ALF model was established by combination of lipopolysaccharide and D-aminogalactose intraperitoneal injection, and early intraperitoneal ACY1215 injection was carried out as intervention. Histopathological examination was performed. Hepatic expression of malate dehydrogenase 1 (MDH1),isocitrate dehydrogenase (IDH1),and fructose-2,6-bisphosphatase 2 (PFKFB2) as well as interleukin-1β (IL-1β) and IL-18 were detected by Western blot. Results Histopathological examination demonstrated the ALF model was successfully established, and ACY1215 intervention greatly ameliorate liver injuries; serum ALT, AST and total bilirubin levels in the model group were (3743.5±655.9)U/L, (2539.4±488.1)U/L and (89.56±7.2)μmol/L, significantly higher than [(34.5±7.6)U/L, (32.3±9.3)U/L and (6.2±2.4)μmol/L, respectively, P < 0.05] in the control, while ACY1215 intervention greatly decreased those parameters, e.g., (951.5±328.9)U/L, (475.3±131.24)U/L and (38.41±9.5)μmol/L (P<0.05); hepatic expression of MDH1 and IDH1 in the model was obviously weaker, that of PFKFB2, IL-18 and IL-1β was greatly intensified as compared to in the control, while in ACY1215-intervende group, the expression of MDH1 and IDH1 intensified, and PFKFB2, IL-18 and IL-1β weakened compared to in the model group. Conclusion The histone deacetylase inhibitor, ACY1215, could have a protective effects on mice with ALF, the mechanism by which it exert might be related to regulation of energy metabolism enzymes.

Key words: Acute liver failure, Histone deacetylase inhibitor, Lipopolysaccharide/D-aminogalactose, Malate dehydrogenase 1, Isocitrate dehydrogenase 1, Fructose-2,6-bisphosphatase 2, Mice