Cafestol preconditioning attenuates apoptosis and autophagy during hepatic ischemia-reperfusion injury by inhibiting ERK/PPARgamma pathway.

OBJECTIVE: The study was aimed to explore the hepatocellular protective functions of cafestol during hepatic ischemia-reperfusion injury and the possible mechanisms. METHODS: Ninety male Balb/c mice were randomly divided into seven groups, including normal control group, L-cafestol(20mg/kg) group, H-cafestol(40mg/kg) group, sham group, IR group, L-cafestol(20mg/kg) + IR group, H-cafestol(40mg/kg) + IR group. Serum liver enzymes (ALT, AST), inflammation mediators, proteins associated with apoptosis and autophagy, indicators linked with ERK/PPARgamma pathway, and liver histopathology were measured using ELISA, qRT-PCR, immunohistochemical staining, and western blotting at 2, 8, and 24 hours after reperfusion. RESULTS: Our findings confirmed that cafestol preconditioning groups could reduce the levels of ALT and AST, alleviate liver pathological damage, suppress the release of inflammation mediators, inhibit the production of pro-apoptosis protein including caspase-3, caspase-9 and Bax, decrease the expression of autophagy-linked protein including Beclin-1 and LC3, increase anti-apoptosis protein Bcl-2, and restrain the activation of ERK and PPARgamma. CONCLUSION: Cafestol preconditioning could attenuate inflammatory response, apoptosis and autophagy on hepatic ischemia reperfusion injury by suppressing ERK/PPARgamma pathway.