Molecular hydrogen attenuates hypoxia/reoxygenation injury of intrahepatic cholangiocytes by activating Nrf2 expression.
Hypoxia/reoxygenation (H/R) injury of cholangiocytes causes serious biliary complications during hepatobiliary surgeries. Molecular hydrogen (H2) has been shown to be effective in protecting various cells and organs against oxidative stress injury. Human liver cholangiocytes were used to determine the potential protective effects of hydrogen against cholangiocyte H/R injury and explore the underlying mechanisms. We found that H2 ameliorated H/R-induced cholangiocytes apoptosis. Our study revealed that H2 activated NF-E2-related factor 2 (Nrf2) and downstream cytoprotective protein expression. However, the protective function of H2 was abolished when Nrf2 was silenced. Apoptosis in cholangiocytes isolated from a rat model of liver ischemia/reperfusion injury indicated that H2 significantly attenuates ischemia/reperfusion cholangiocyte injury in vivo. In conclusion, our study shows that H2 protects intrahepatic cholangiocytes from hypoxia/reoxygenation-induced apoptosis in vitro or in vivo, and this phenomenon may depend on activating Nrf2 expression.
Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China.
Jianhua
J
Yu
Department of Cardiology, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China.
Weiguang
W
Zhang
Department of Rehabilitation, Heilongjiang Agricultural Reclamation General Hospital, Harbin, China.
Rongguo
R
Zhang
Department of Hepatopancreatobiliary Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Guixing
G
Jiang
Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China.
Haijun
H
Tang
Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China.
Xinxian
X
Ruan
Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China.
Peitu
P
Ren
Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China. Electronic address: sygd_lbc@126.com.
Baochun
B
Lu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001653:Bile Ducts, Intrahepatic / Q000098:blood supply / Q000473:pathology*; D020868:Gene Silencing; D006859:Hydrogen / Q000494:pharmacology / Q000627:therapeutic use*; D008107:Liver Diseases / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D015398:Signal Transduction
D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D006859:Hydrogen
Hypoxia/reoxygenation; Intrahepatic cholangiocytes; Ischemia/reperfusion; Molecular hydrogen; NF-E2-related factor 2; Oxidative stress