Postbinge effects of acute alcohol intoxication on hepatic free radical formation.
The present studies were performed to test the hypothesis that Kupffer and endothelial cells are activated after recovery from an acute alcohol binge, which is accompanied by formation of oxygen-derived radicals. These radicals have been implicated in the pathogenesis of alcohol-mediated tissue injury in a number of organs. Male Sprague-Dawley rats received an intravenous injection of 20% ethanol in saline (1.75 g/kg), followed by an intravenous infusion (250 to 300 mg/kg/hr) for 12 hr. At the end of 12-hr infusion, ethanol was replaced by saline, and the infusion was continued for a further 6 hr. This was referred to as the recovery period. The 6-hr recovery period was selected because superoxide anion generation by the perfused liver peaked at this time point. Superoxide anion formation by the perfused liver was measured by the superoxide dismutase-inhibitable reduction of ferricytochrome c. Kupffer and endothelial cells were isolated for the determination of in vivo glucose uptake and in vitro superoxide anion release. Results show that a significant (p < 0.05) amount of superoxide (1.54 nmol/min/g) was generated by the perfused liver at 6 hr recovery after 12 hr of ethanol infusion. Serum ALT activity was also elevated in this treatment group. Time-matched control-saline infused animals or ethanol-treated animals without a recovery period released < 0.2 nmol/min/g of superoxide. The postrecovery superoxide production and an accompanying increase in the in vivo glucose uptake were also observed in isolated Kupffer and endothelial cells. Depletion of Kupffer cells by gadolinium chloride before ethanol treatment and recovery was associated with significant attenuation of free radical formation by the perfused liver and reduction of serum ALT. These studies demonstrate that recovery from an acute alcohol binge has a stimulating effect on hepatic sinusoidal superoxide production, and it may also affect liver function.
Bautista
A P
AP
Department of Physiology and Alcohol Research Center, Louisiana State University Medical Center, New Orleans 70112, USA.
Spitzer
J J
JJ
D000435:Alcoholic Intoxication / Q000473:pathology*; D000818:Animals; D002478:Cells, Cultured; D004727:Endothelium / Q000473:pathology; D005609:Free Radicals; D007728:Kupffer Cells / Q000473:pathology; D008099:Liver / Q000473:pathology*; D008108:Liver Diseases, Alcoholic / Q000473:pathology; D008297:Male; D010477:Perfusion; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
D005609:Free Radicals; D017382:Reactive Oxygen Species; D013481:Superoxides