title: 5-Aminolevulinic acid combined with ferrous iron ameliorate ischemia-reperfusion injury in the mouse fatty liver model.
abstract: BACKGROUND
  The fatty liver could increase the risk of serious acute ischemia reperfusion (I/R) injury, and hepatic steatosis is indeed a major risk factor for hepatic failure after grafting a fatty liver.
  
  
  METHODS
  Fatty liver models of methionine- and choline-deficient high-fat mice were subjected to I/R injury with or without 5-aminolevulinic acid (5-ALA)/sodium ferrous citrate (SFC) treatment. Levels of hepatic enzymes, lipid peroxidation and apoptosis, inflammatory cytokines and heme oxygenase (HO)-1, and the carbon monoxide (CO) in the liver, and reactive oxygen species (ROS), inflammatory cytokines and members of the signaling pathway in isolated Kupffer were assessed.
  
  
  RESULTS
  Alanine aminotransferase and aspartate aminotransferase levels, the number of necrotic areas, thiobarbituric acid reactive substance content, TUNEL-positive cells, infiltrated macrophages, and the inflammatory cytokine expression after I/R injury were dramatically decreased, whereas the endogenous CO concentrations and the HO-1 expression were significantly increased by 5-ALA/SFC treatment. The expression of toll-like receptors 2 and 4, NF-κB and inflammatory cytokines and ROS production in Kupffer cells were significantly decreased with 5-ALA/SFC treatment.
  
  
  CONCLUSIONS
  5-ALA/SFC significantly attenuates the injury level in the fatty liver after I/R injury.
authors.affiliation: Division of Transplantation Immunology, National Institute for Child Health and Development, Tokyo, Japan; Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Osaka, Japan; Second Department of Surgery, University of Toyama, Toyama, Japan; Clinical Medicine Research Center of Affiliated Hospital, Inner Mongolia Medical University, Hohhot, China.
authors.forename: Shaowei
authors.initials: S
authors.lastname: Li
authors.affiliation: Third Department of Internal Medicine, University of Toyama, Toyama, Japan. Electronic address: terutaka-tym@umin.ac.jp.
authors.forename: Terumi
authors.initials: T
authors.lastname: Takahara
authors.affiliation: Division of Transplantation Immunology, National Institute for Child Health and Development, Tokyo, Japan. Electronic address: ri-k@ncchd.go.jp.
authors.forename: Xiao-Kang
authors.initials: XK
authors.lastname: Li
authors.affiliation: Division of Transplantation Immunology, National Institute for Child Health and Development, Tokyo, Japan; AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujino
authors.affiliation: Third Department of Internal Medicine, University of Toyama, Toyama, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sugiyama
authors.affiliation: Second Department of Surgery, University of Toyama, Toyama, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsukada
authors.affiliation: Division of Transplantation Immunology, National Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Chi
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Specific Organ Regulation (Urology), Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kakuta
authors.affiliation: Department of Specific Organ Regulation (Urology), Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Nonomura
authors.affiliation: SBI Pharmaceuticals Co., Ltd., Tokyo, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ito
authors.affiliation: SBI Pharmaceuticals Co., Ltd., Tokyo, Japan.
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: SBI Pharmaceuticals Co., Ltd., Tokyo, Japan.
authors.forename: Motowo
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: SBI Pharmaceuticals Co., Ltd., Tokyo, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Takahara
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage*; D000818:Animals; D016207:Cytokines / Q000276:immunology; D004338:Drug Combinations; D005234:Fatty Liver / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D005296:Ferrous Compounds / Q000008:administration & dosage*; D007728:Kupffer Cells / Q000187:drug effects / Q000276:immunology; D051379:Mice; D017382:Reactive Oxygen Species / Q000276:immunology; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D004338:Drug Combinations; D005296:Ferrous Compounds; D017382:Reactive Oxygen Species; C020748:ferrous sulfate; D000622:Aminolevulinic Acid
keywords: 5-Aminolevulinic acid; Carbon monoxide; Fatty liver; Hemeoxygenase-1; Ischemia-reperfusion injury; Oxidative stress