Propofol attenuates inflammatory response and apoptosis to protect d-galactosamine/lipopolysaccharide induced acute liver injury via regulating TLR4/NF-κB/NLRP3 pathway

Abstract

Objective: Propofol has been reported to be protective against liver injury due to its anti-inflammatory, anti-oxidative and anti-apoptotic activities. The purpose of this study was to examine the protective effects of propofol on d-galactosamine/lipopolysaccharide (d-GalN/LPS) induced acute liver injury.

Methods: Mice were given an intraperitoneal injection of propofol before d-GalN/LPS treatment. Liver injury was confirmed by serum biochemical analysis and liver histopathological analysis. Relevant molecular events were determined by ELISA, western blot, and test kits. Cell apoptosis were evaluated by TUNEL assay.

Results: The results showed that propofol significantly prevented d-GalN/LPS-induced liver damage by preventing associated increases of serum alanine transaminase (ALT) and aspartate transaminase (AST) and restoring liver histopathological changes. Propofol markedly inhibited the production of inflammatory cytokines and oxidative stress-related factors. Propofol markedly reduced hepatocyte apoptosis, decreased Bax, Bad, cleaved caspase-3 and increased Bcl-2 expression. Besides, NLRP3 inflammasome and TLR4/NF-κB pathway were inactivated under the treatment of propofol according to the expression of pathways-related proteins.

Conclusion: Taken together, propofol contributed to liver protection against d-GalN/LPS-induced liver injury in mice by inhibiting inflammation, oxidative stress and hepatocyte apoptosis through regulating TLR4/NF-κB/NLRP3 pathway.

Keywords: Acute liver injury; NLRP3 inflammasome; Propofol; TLR4/NF-κB; d-galactosamine/lipopolysaccharide.