R. Thomas Gentry

Metabolism of ethanol in rat gastric cells and its inhibition by cimetidine

BACKGROUND/AIMS Several studies have shown that the stomach has sufficient alcohol dehydrogenase activity to metabolize a significant amount of alcohol and that cimetidine depresses this alcohol dehydrogenase activity. However, both gastric metabolism of ethanol and its inhibition by cimetidine remain controversial. Given the difficulty in assessing gastric metabolism of ethanol in vivo, this subject was investigated in vitro. METHODS Cultured rat gastric epithelial cells were incubated with 200 mmol/L [1-14C]ethanol for 90 minutes with and without cimetidine (0.1-1 mmol/L) or omeprazole (1 mmol/L). The quantity of ethanol oxidized by gastric cells was measured by the amount of acetate produced using ion exchange chromatography. RESULTS The majority of cells at confluency had typical features of mucous cells. The gastric cells metabolized significant amounts of ethanol, sufficient to account for in vivo first-pass metabolism of ethanol in rats. Cimetidine, but not omeprazole, reduced ethanol metabolism by 39.9% +/- 4.9% (P < 0.01), an inhibition comparable with that previously reported for first-pass metabolism in vivo. CONCLUSIONS Gastric cells in tissue culture are capable of significant ethanol oxidation, the in vitro rates are sufficient to account for first-pass metabolism of ethanol in vivo, and cimetidine inhibits ethanol metabolism in tissue culture, an effect that parallels its decrease of first-pass metabolism in vivo.

Mechanism of the aspirin-induced rise in blood alcohol levels.

Aspirin increases blood alcohol levels after post-prandial alcohol consumption in men. This was attributed to a decrease in first pass metabolism secondary to inhibition of gastric alcohol dehydrogenase. Since accelerated gastric emptying, decreased volume of distribution or delayed elimination could also result in higher blood alcohol levels, we investigated the effect of aspirin (1 g taken with a meal) on these parameters. Aspirin did not change the volume of ethanol distribution or the rate of its elimination. Moreover, it did not have a significant effect on gastric emptying. The half-time of 99Tc-DTPA loss was 65.5+/-5.4 minutes without and 71.3+/-6.5, with aspirin. Despite a trend for slower gastric emptying with aspirin, the alcohol bioavailability increased and was associated with a 39% decrease in the first pass metabolism of alcohol (from 106+/-4 to 65+/-19 mg/kg, p<0.05), consistent with the inhibition of gastric ADH activity. In keeping with this interpretation, the effect of aspirin was virtually absent in women, who have a much smaller first pass metabolism available for inhibition by aspirin.

Gastric metabolism of ethanol in Syrian golden hamster

First-pass metabolism (FPM) of orally ingested alcohol has been attributed to gastric alcohol dehydrogenase (ADH) activity in both humans and rats. To determine whether gastric alcohol dehydrogenase is essential for alcohol FPM, we sought a species lacking this enzyme. We found that Syrian golden hamsters have negligible gastric ADH yet alcohol FPM (265±25 mg ethanol/kg) was comparable to that of rats (251±31 mg/kg). To determine whether hamster gastric mucosal cells metabolize sufficient alcohol to account for this FPM, primary cultures were established, and these cells metabolized 1.99±0.84 μmol ethanol/106 cells/hr, an amount sufficient to account for the bulk of alcohol FPM. In contrast to alcohol dehydrogenase, catalase activity in hamster gastric mucosa (870±93 units/g tissue) was eightfold higher than in rat gastric mucosa (111±9 units/g tissue;P<0.0001). FPM in hamsters treated with 3-aminotriazole was reduced from 242±24 to 130±22 mg/kg (P<0.05) but was not reduced in rats. The results imply that catalase participates in gastric alcohol metabolism of hamsters.