Abstract: Objective The purpose of this experiment was to investigate the protective effect of histone deacetylase (HDAC) inhibitor ACY1215 on acute liver failure (ALF) in mice and to explore its possible mechanism. Methods 18 mice were randomly divided into control, model and ACY1215-intervened group, with 6 in each. The ALF model was induced by intraperitoneal injection of lipopolysaccharide (LPS) and D-galactosamine (D-Gal). Liver tissue PANoptosis associated protein expression, such as receptor-interacting serine-threonine kinase 1(RIPK1), gas derivative D protein (GSDMD), Caspase-3, Caspase-8 and mixed lineage kinase domain protein (ML) were detected by Western blot. Results Liver histopathological examination showed that disordered intrahepatic parenchymal cell arrangement, with lamellar cell necrosis, a large number of blood cell exudation, and inflammatory cell infiltration in ALF group, while liver tissue damage alleviated in ACY1215-intervened group; serum ALT, AST and total bilirubin levels in ALF group were (3279.8±639.0)U/L,(2510.1±383.2)U/L and (85.5±6.8)μmol/L, while they all decreased to [(987.6±254.3)U/L, (426.3±105.6)U/L and (38.1±8.9)μmol/L, respectively, P<0.05] in ACY1215-intervened group; intrahepatic tissue PANoptosis-related protein, such as RIPK1, GSDMD, Caspase-3, Caspase-8 and MLKL intensified in ALF group, while they all obviously weakened in ACY1215-intervened group (P<0.05). Conclusion Histone deacetylase inhibitor ACY1215 could play a protective role in mice with ALF, probably by regulating PANoptosis-related protein expression.

Key words: Acute liver failure, Histone deacetylase inhibitors, ACY1215, PANoptosis