title: Remote ischemic conditioning protects against acetaminophen-induced acute liver injury in mice.
abstract: OBJECTIVE
  Acetaminophen (APAP) overdose is a major cause of drug-induced acute liver failure. Studies have shown that remote ischemic pre- and post-conditioning (R-IPC and R-IPOST) can protect the liver against ischemia-reperfusion (I/R) and lipopolysaccharide-induced injuries. The aim of this study was to investigate the effect of R-IPC and R-IPOST on APAP-induced hepatotoxicity in mice.
  
  
  METHODS
  Mice were randomized (n = 6 per group) to seven major groups: (i) normal control; (ii) sham operated; (iii) APAP; (iv) R-IPC + APAP; (v) R-IPC + APAP + zinc protoporphyrin (ZnPP); (vi) R-IPOST + APAP; and (vii) R-IPOST + APAP + ZnPP. Sixteen hours after APAP treatment, mouse liver and serum were collected to determine the severity of liver injury.
  
  
  RESULTS
  The results showed that R-IPC and R-IPOST significantly decreased APAP-induced serum levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, interleukin-6, and hepatic malondialdehyde, as well as nitrotyrosine formation. Both R-IPC and R-IPOST could improve the hepatic superoxide dismutase, glutathione, and glutathione peroxidase activities and depress the expressions of pro-inflammatory associated proteins, such as inducible nitric oxide synthetase and nuclear factor-κB. They could also increase heme oxygenase-1 expression; however, ZnPP could counteract this protective effect.
  
  
  CONCLUSIONS
  Remote ischemic conditioning has significant therapeutic potential in APAP-induced hepatotoxicity by inhibiting oxidative stress and inflammation and promoting heme oxygenase-1 expression.
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University.|Department of Hepatobiliary Surgery, Shaanxi Provincial People's Hospital.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Hepatobiliary Surgery, Shaanxi Provincial People's Hospital.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University.
authors.forename: Sushun
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Bi
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University.
authors.forename: Jingyao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, Shaanxi Provincial People's Hospital.
authors.forename: Lixue
authors.initials: L
authors.lastname: Du
authors.affiliation: Department of Renal Transplantation, Hospital of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
keywords: HO-1; R-IPC; R-IPOST; acetaminophen; inflammation; reactive oxygen species