title: Ascorbic acid deficiency increases endotoxin influx to portal blood and liver inflammatory gene expressions in ODS rats.
abstract: OBJECTIVE
  The aim of this study was to determine whether ascorbic acid (AsA) deficiency-induced endotoxin influx into portal blood from the gastrointestinal tract contributes to the inflammatory changes in the liver.
  
  
  METHODS
  The mechanisms by which AsA deficiency provokes inflammatory changes in the liver were investigated in Osteogenic Disorder Shionogi (ODS) rats (which are unable to synthesize AsA). Male ODS rats (6-wk-old) were fed a diet containing sufficient (300 mg/kg) AsA (control group) or a diet without AsA (AsA-deficient group) for 14 or 18 d.
  
  
  RESULTS
  On day 14, the hepatic mRNA levels of acute-phase proteins and inflammation-related genes were significantly higher in the AsA-deficient group than the control group, and these elevations by AsA deficiency were exacerbated on day 18. The serum concentrations of interleukin (IL)-1β and IL-6, which induce acute-phase proteins in the liver, were also significantly elevated on day 14 in the AsA-deficient group compared with the respective values in the control group. IL-1β mRNA levels in the liver, spleen, and lung were increased by AsA deficiency. Moreover, on both days 14 and 18, the portal blood endotoxin concentration was significantly higher in the AsA-deficient group than in the control group, and a significant correlation between serum IL-1β concentrations and portal endotoxin concentrations was found in AsA-deficient rats. In the histologic analysis of the ileum tissues, the number of goblet cells per villi was increased by AsA deficiency.
  
  
  CONCLUSIONS
  These results suggest that AsA deficiency-induced endotoxin influx into portal blood from the gastrointestinal tract contributes to the inflammatory changes in the liver.
authors.affiliation: Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tokuda
authors.affiliation: Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Miura
authors.affiliation: Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hoshinaga
authors.affiliation: Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Murai
authors.affiliation: Toxicology Division, Institute of Environmental Toxicology, Ibaraki, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Aoyama
authors.affiliation: Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University, Shizuoka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ito
authors.affiliation: Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University, Shizuoka, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Morita
authors.affiliation: Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan. Electronic address: horiof@agr.nagoya-u.ac.jp.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Horio
mesh_terms: D000818:Animals; D001206:Ascorbic Acid Deficiency / Q000097:blood*; D019446:Endotoxemia / Q000473:pathology; D004731:Endotoxins / Q000097:blood*; D007082:Ileum / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D053583:Interleukin-1beta / Q000097:blood / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000503:physiopathology*; D008107:Liver Diseases / Q000473:pathology; D008168:Lung / Q000378:metabolism; D008297:Male; D009929:Organ Size; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013154:Spleen / Q000378:metabolism
chemical_list: D004731:Endotoxins; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger
keywords: Acute-phase proteins; Ascorbic acid; Ascorbic acid deficiency; Endotoxin; Hepatic inflammation; Inflammatory cytokines; ODS rat