Kupffer cell depletion attenuates superoxide anion release into the hepatic sinusoids after lipopolysaccharide treatment.
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.
Fukuda
Masahiko
M
Department of Internal Medicine, School of Medicine, Keio University, Japan.
Yokoyama
Hirokazu
H
Mizukami
Takeshi
T
Ohgo
Hideki
H
Okamura
Yukishige
Y
Kamegaya
Yoshitaka
Y
Horie
Yoshinori
Y
Kato
Shinzo
S
Ishii
Hiromasa
H
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*
D000975:Antioxidants; D008070:Lipopolysaccharides; D013481:Superoxides; D005682:Gadolinium; C038958:gadolinium chloride