Superoxide anion release into the hepatic sinusoid after an acute ethanol challenge and its attenuation by Kupffer cell depletion

Superoxide anion release into the hepatic sinusoids and subsequent damage t o the endothelial cells of the hepatic sinusoids after ethanol challenge wa s examined. A 250 mg/kg body weight/hr dose of ethanol was given to rats fo r 3 hr, and superoxide anion release into the hepatic sinusoids was examine d in a liver perfusion model using the cytochrome c method. Ethanol treatme nt resulted in superoxide anion release into the hepatic sinusoids (0.20 +/ - 0.01 vs. 0.12 +/- 0.02 o.d., p < 0.05) and an increase in the purine nucl eoside phosphorylase/alanine aminotransferase ratio in the liver perfusate, a marker of damage to the endothelial cells of the hepatic sinusoids (0.00 3 +/- 0.002 vs. 0.008 +/- 0.002; p < 0.05). Tumor necrosis factor-alpha was not detectable in either group, and there were no significant differences in the population of hepatic macrophages, leukocytes, or Kupffer cells betw een the two groups. To clarify the role of Kupffer cells in the mechanism, 10 mg/kg of body weight of gadolinium chloride was given to rats twice, 24 hr apart, resulting in depletion of ED2-positive cells from the hepatic lob ules. The superoxide anion release after the ethanol challenge was signific antly attenuated in the Kupffer cell-depleted rats, compared with the contr ols (0.14 +/- 0.02; p < 0.05, compared with ethanol alone). The change was associated with a significant decrease in the purine nucleoside phosphoryla se/alanine aminotransferase ratio in the liver perfusate (0.004 +/- 0.002; p < 0.05, compared with ethanol alone). Ethanol causes superoxide anion rel ease into the hepatic sinusoid and subsequent damage to the sinusoidal endo thelial cells, These changes were reduced by Kupffer cell depletion. This s upports the view that Kupffer cell depletion has a protective effect on eth anol-induced liver injury.