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 alco hol binge, which is accompanied by formation of oxygen-derived radical s. 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 th e infusion was continued for a further 6 hr. This was referred to as t he recovery period. The 6-hr recovery period was selected because supe roxide anion generation by the perfused liver peaked at this time poin t. Superoxide anion formation by the perfused liver was measured by th e superoxide dismutase-inhibitable reduction of ferricytochrome c. Kup ffer and endothelial cells were isolated for the determination of in v ivo 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 et hanol 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 superox ide. The postrecovery superoxide production and an accompanying increa se in the in vivo glucose uptake were also observed in isolated Kupffe r and endothelial cells. Depletion of Kupffer cells by gadolinium chlo ride before ethanol treatment and recovery was associated with signifi cant attenuation of free radical formation by the perfused liver and r eduction of serum ALT. These studies demonstrate that recovery from an acute alcohol binge has a stimulating effect on hepatic sinusoidal su peroxide production, and it may also affect liver function.