title: Edaravone prevents lung injury induced by hepatic ischemia-reperfusion.
abstract: BACKGROUND
  Lung injury is a major clinical concern after hepatic ischemia-reperfusion (I/R), due to the production of reactive oxygen species in the reperfused liver. We investigated the efficacy of edaravone, a potent free-radical scavenger, for attenuating lung injury after hepatic I/R.
  
  
  METHODS
  Adult male Sprague-Dawley rats were assigned to sham + normal saline (NS), I/R + NS, or I/R + edaravone group. Rats in the I/R groups were subjected to 90 min of partial hepatic I/R. Five minutes before reperfusion, 3 mg/kg edaravone was administered to the I/R + edaravone group. After 6 h of reperfusion, we evaluated lung histopathology and wet-to-dry ratio. We also measured malondialdehyde (MDA), an indicator of oxidative stress, in the liver and the lung, as well as cytokine messenger RNA expressions in the reperfused liver and plasma cytokine concentrations.
  
  
  RESULTS
  Histopathology revealed lung damages after 6 h reperfusion of partial ischemic liver. Moreover, a significant increase in lung wet-to-dry ratio was observed. MDA concentration increased in the reperfused liver, but not in the lungs. Edaravone administration attenuated the lung injury and the increase of MDA in the reperfused liver. Edaravone also suppressed the reperfusion-induced increase of interleukin-6 messenger RNA expressions in the liver and plasma interleukin-6 concentrations.
  
  
  CONCLUSIONS
  Edaravone administration before reperfusion of the ischemic liver attenuates oxidative stress in the reperfused liver and the subsequent lung injury. Edaravone may be beneficial for preventing lung injury induced by hepatic I/R.
authors.affiliation: Department of Emergency Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
authors.forename: Munehito
authors.initials: M
authors.lastname: Uchiyama
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tojo
authors.affiliation: Department of Diagnostic Pathology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Yazawa
authors.affiliation: Department of Palliative Care Medicine, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Ota
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Goto
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan. Electronic address: kiyok@med.yokohama-cu.ac.jp.
authors.forename: Kiyoyasu
authors.initials: K
authors.lastname: Kurahashi
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D016207:Cytokines / Q000097:blood; D004353:Drug Evaluation, Preclinical; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D008099:Liver / Q000098:blood supply* / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*
chemical_list: D016207:Cytokines; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000077553:Edaravone; D000983:Antipyrine
keywords: Cytokine; Free radical-scavenger; Hepatic ischemia–reperfusion; Liver injury; Lung injury; Reactive oxygen species