title: Alpha-lipoic acid exerts a liver-protective effect in acute liver injury rats.
abstract: BACKGROUND
  Recent evidence indicates that alpha-lipoic acid (α-LA) has a variety of liver-protective effects through the suppression of inflammatory mediators including tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS). However, there are few reports that α-LA markedly enhanced the survival rate in animal models of liver injury with more than 90% death. The aim of this study was to investigate the beneficial effects of α-LA in a rat model of acute liver injury and to clarify the mechanisms of α-LA action.
  
  
  METHODS
  Rats were treated with d-galactosamine and lipopolysaccharide (GalN and LPS) to induce acute liver injury. α-LA (100 mg/kg) was administered intraperitoneally 1 h before GalN and LPS injection. Inflammatory mediators including TNF-α and iNOS were analyzed.
  
  
  RESULTS
  A single injection of α-LA improved the survival rate by more than 80%. α-LA prevented serum transaminase increases, histopathologic changes, and apoptosis in the liver. In the serum, α-LA decreased TNF-α production and increased interleukin (IL)-10 production. In the liver, α-LA reduced TNF-α and IL-6 messenger RNA (mRNA) but enhanced IL-10 mRNA. α-LA decreased the expression of iNOS mRNA and its antisense transcript, leading to the reduction of iNOS protein expression and resulting in the inhibition of nitric oxide production. An electrophoretic mobility shift assay revealed that α-LA reduced the activation of nuclear factor-kappa B induced by GalN and LPS.
  
  
  CONCLUSIONS
  α-LA inhibited the induction of inflammatory mediators, such as TNF-α and iNOS, in part through the inhibition of nuclear factor-kappa B activation and enhanced the induction of IL-10. α-LA may have therapeutic potential for use in the prevention of acute liver injury.
authors.affiliation: Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kaibori
authors.affiliation: Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Miki
authors.affiliation: Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan.
authors.forename: Richi
authors.initials: R
authors.lastname: Nakatake
authors.affiliation: Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan.
authors.forename: Katsuji
authors.initials: K
authors.lastname: Tokuhara
authors.affiliation: Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, Kusatsu, Shiga, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Nishizawa
authors.affiliation: Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan; Research Organization of Science and Technology, Ritsumeikan University, Kusatsu, Shiga, Japan. Electronic address: okumura@hirakata.kmu.ac.jp.
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Okumura
authors.affiliation: Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan.
authors.forename: A-Hon
authors.initials: AH
authors.lastname: Kwon
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D004353:Drug Evaluation, Preclinical; D005688:Galactosamine; D016753:Interleukin-10 / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D008063:Thioctic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D008063:Thioctic Acid; D005688:Galactosamine; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat
keywords: Acute liver injury; Inducible nitric oxide synthase; Interleukin-10; Nuclear factor-κB; Tumor necrosis factor-α; d-galactosamine and lipopolysaccharide