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

Abstract

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/PPARγ 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 PPARγ.

CONCLUSION:

Cafestol preconditioning could attenuate inflammatory response, apoptosis and autophagy on hepatic ischemia reperfusion injury by suppressing ERK/PPARγ pathway.

• Authors: Jie Ji, Liwei Wu, Jiao Feng, Wenhui Mo, Jianye Wu, Qiang Yu, Sainan Li, Jie Zhang, Weiqi Dai, Xuanfu Xu, Yuqing Mao, Shizan Xu, Kan Chen, Jingjing Li, Chuanyong Guo
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 84 Pg. 106529 (Jul 2020) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 32344356 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Apoptosis Regulatory Proteins
• Diterpenes
• IL1B protein, mouse
• Interleukin-1beta
• PPAR gamma
• Protective Agents
• Tnf protein, mouse
• Tumor Necrosis Factor-alpha
• cafestol

Topics

• Animals
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Cells, Cultured
• Diterpenes (administration & dosage)
• Hepatocytes (drug effects, metabolism)
• Interleukin-1beta (genetics, metabolism)
• Liver (blood supply, drug effects, metabolism, pathology)
• Liver Diseases (drug therapy, genetics, metabolism, pathology)
• MAP Kinase Signaling System (drug effects)
• Male
• Mice, Inbred BALB C
• PPAR gamma (genetics, metabolism)
• Protective Agents (administration & dosage)
• Reperfusion Injury (drug therapy, genetics, metabolism, pathology)
• Tumor Necrosis Factor-alpha (genetics, metabolism)