Jie Ji1, Liwei Wu1, Jiao Feng1, Wenhui Mo2, Jianye Wu3, Qiang Yu1, Sainan Li1, Jie Zhang4, Weiqi Dai5, Xuanfu Xu2, Yuqing Mao6, Shizan Xu7, Kan Chen1, Jingjing Li8, Chuanyong Guo9. 1. Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. 2. Department of Gastroenterology, Shidong Hospital of Shanghai, Shanghai 200433, China. 3. Department of Gastroenterology, Putuo People's Hospital, Tongji University School of Medicine, Shanghai 200060, China. 4. Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Shanghai Tenth Hospital, School of Clinical Medicine of Nanjing Medical University, Shanghai 200072, China. 5. Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Department of Gastroenterology, Putuo People's Hospital, Tongji University School of Medicine, Shanghai 200060, China; Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai 200032, China; Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai, 200032, China; Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200336, China. 6. Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China. 7. Department of Gastroenterology, Jinshan Hospital of Fudan University, Jinshan, Shanghai 201508, China. 8. Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Department of Gastroenterology, Putuo People's Hospital, Tongji University School of Medicine, Shanghai 200060, China. Electronic address: sealjj@126.com. 9. Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: guochuanyong@hotmail.com.
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.
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: Ana Isabel Álvarez-Mercado; Carlos Rojano-Alfonso; Marc Micó-Carnero; Albert Caballeria-Casals; Carmen Peralta; Araní Casillas-Ramírez Journal: Front Cell Dev Biol Date: 2021-06-01