Fucoidan Ameliorates Ferroptosis in Ischemia-reperfusion-induced Liver Injury through Nrf2/HO-1/GPX4 Activation  

作　　者：Jing-Jing Li Wei-Qi Dai Wen-Hui Mo Wen-Qiang Xu Yue-Yue Li Chuan-Yong Guo Xuan-Fu Xu 

机构地区：[1]Department of Gastroenterology,Shidong Hospital of Shanghai,Shanghai,China [2]Department of Gastroenterology,Shanghai Tenth People’s Hospital,Tongji University School of Medicine,Shanghai,China

出　　处：《Journal of Clinical and Translational Hepatology》2023年第6期1341-1354,共14页临床与转化肝病杂志（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.82100638,81772591);Shanghai Municipal Commission of Health and Family Planning(No.201740156);the Shanghai Sailing Program(No.20YF1443300).

摘　　要：Background and Aims:Liver ischemia-reperfusion(IR)injury is a common pathological process in liver surgery.Ferroptosis,which is closely related to lipid peroxidation,has recently been confirmed to be involved in the pathogenesis of IR injury.However,the development of drugs that regulate ferroptosis has been slow,and a complete understanding of the mechanisms underlying ferroptosis has not yet been achieved.Fucoidan(Fu)is a sulfated polysaccharide that has attracted research interest due to its advantages of easy access and wide biological activity.Methods:In this study,we established models of IR injury using erastin as an activator of ferroptosis,with the ferroptosis inhibitor ferrostatin-1(Fer-1)as the control.We clarified the molecular mechanism of fucoidan in IR-induced ferroptosis by determining lipid peroxidation levels,mitochondrial morphology,and key pathways in theta were involved.Results:Ferroptosis was closely related to IR-induced hepatocyte injury.The use of fucoidan or Fer-1 inhibited ferroptosis by eliminating reactive oxygen species and inhibiting lipid peroxidation and iron accumulation,while those effects were reversed after treatment with erastin.Iron accumulation,mitochondrial membrane rupture,and active oxygen generation related to ferroptosis also inhibited the entry of nuclear factor erythroid 2-related factor 2(Nrf2)into the nucleus and reduced downstream heme oxygenase-1(HO-1)and glutathione peroxidase 4(GPX4)protein levels.However,fucoidan pretreatment produced adaptive changes that reduced irreversible cell damage induced by IR or erastin.Conclusions:Fucoidan inhibited ferroptosis in liver IR injury via the Nrf2/HO-1/GPX4 axis.

关 键 词：FUCOIDAN ISCHEMIA-REPERFUSION Ferroptosis Lipid peroxidation NRF2 

分 类 号：R575[医药卫生—消化系统]