title: Effects of globin digest and its active ingredient Trp-Thr-Gln-Arg on galactosamine/lipopolysaccharide-induced liver injury in ICR mice.
abstract: OBJECTIVE
  We investigated the effects of globin digest (GD) and its active ingredient Trp-Thr-Gln-Arg (WTQR) on galactosamine/lipopolysaccharide (GalN/LPS)-induced liver injury in imprinting control region (ICR) mice.
  
  
  METHODS
  The effects of WTQR and GD on the liver injury were examined by measuring the survival rate, serum aminotransferase activities, hepatic components, antioxidant enzyme activities, histopathological analysis, serum levels and hepatic gene expression of tumor necrosis factor-alpha (TNF-α), macrophage inflammatory protein-2 (MIP-2), and nitric oxide (NO) or inducible nitric oxide synthase (iNOS), and nuclear factor-kappa B (NF-κB) p65 content in GalN/LPS-treated ICR mice. RAW264 mouse macrophages were used to confirm the anti-inflammatory effects of WTQR and GD on the macrophages.
  
  
  RESULTS
  WTQR and GD increased the survival rate, suppressed the serum aminotransferase activities, serum levels and hepatic gene expression of TNF-α, MIP-2, and NO or iNOS, and nuclear NF-κB p65 content in GalN/LPS-treated mice; decreased the oxidized glutathione content, increased the superoxide dismutase activity, and decreased the histopathological grade values of the hepatocyte necrosis and lobular inflammation in GalN/LPS-injured liver; and suppressed the release levels and gene expression of TNF-α, MIP-2, and NO or iNOS, and nuclear NF-κB p65 content in LPS-stimulated RAW264 macrophages. WTQR and GD may improve the antioxidant defense system and inflammatory status in GalN/LPS-injured liver.
  
  
  CONCLUSIONS
  These findings indicate that WTQR and GD have hepatoprotective effects on GalN/LPS-induced liver injury in ICR mice.
authors.affiliation: MG Pharma Inc., 7-7-25, Saito-Asagi, Ibaraki, Osaka 567-0085, Japan. y-sasakawa@mgpharma.co.jp
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sasakawa
authors.forename: Akari
authors.initials: A
authors.lastname: Kominami
authors.forename: Kaori
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Fumiko
authors.initials: F
authors.lastname: Nakaoka
authors.forename: Miki
authors.initials: M
authors.lastname: Nakamura
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nakao
authors.forename: Michiyo
authors.initials: M
authors.lastname: Abe
authors.forename: Chizuko
authors.initials: C
authors.lastname: Fukuhama
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Kagawa
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002460:Cell Line; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000097:blood / Q000235:genetics; D005688:Galactosamine / Q000008:administration & dosage / Q000009:adverse effects; D005914:Globins / Q000008:administration & dosage* / Q000737:chemistry; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000009:adverse effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009842:Oligopeptides / Q000008:administration & dosage*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000737:chemistry; D015996:Survival Rate; D000637:Transaminases / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics
chemical_list: D000975:Antioxidants; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009842:Oligopeptides; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D005688:Galactosamine; D005914:Globins; D052247:Nitric Oxide Synthase Type II; D000637:Transaminases