title: Kupffer cell depletion attenuates superoxide anion release into the hepatic sinusoids after lipopolysaccharide treatment.
abstract: OBJECTIVE
  The mechanisms involved in the beneficial effect of gadolinium chloride against endotoxin-induced liver damage were studied.
  
  
  METHODS
  Superoxide anions released into the hepatic sinusoids were examined in a liver perfusion model using the cytochrome C method.
  
  
  RESULTS
  Gadolinium chloride treatment fully depleted ED2-positive cells from the liver and significantly attenuated superoxide anion release after a lipopolysaccharide or tumor necrosis factor-alpha (TNF-alpha) challenge. Moreover, gadolinium chloride treatment resulted in a significant decline in endothelial cell damage in the hepatic sinusoids as assessed by the purine nucleoside phosphorylase/glutamic-pyruvic transaminase ratio in the liver perfusate. Although gadolinium chloride treatment did not affect the level of serum TNF-alpha, it significantly reduced that of interleukin (IL)-8 and neutrophil migration in the hepatic sinusoids after the lipopolysaccharide challenge.
  
  
  CONCLUSIONS
  These data suggest that a reduction of the superoxide anion level in the hepatic sinusoids in acute endotoxemia and subsequent reduction of neutrophil migration into the liver may indicate that gadolinium chloride treatment suppresses the progression of liver damage in acute endotoxemia.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Fukuda
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Yokoyama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mizukami
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohgo
authors.forename: Yukishige
authors.initials: Y
authors.lastname: Okamura
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kamegaya
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Horie
authors.forename: Shinzo
authors.initials: S
authors.lastname: Kato
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Ishii
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D019446:Endotoxemia / Q000378:metabolism; D005682:Gadolinium / Q000494:pharmacology*; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008099:Liver / Q000378:metabolism; D008107:Liver Diseases / Q000209:etiology*; D008297:Male; D023421:Models, Animal; D018384:Oxidative Stress / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D008070:Lipopolysaccharides; D013481:Superoxides; D005682:Gadolinium; C038958:gadolinium chloride