ABSTRACT
BACKGROUND & AIMS: The bioavailability of orally administered alcohol is incomplete, indicating first-pass metabolism. There is debate regarding the site of first-pass metabolism and specifically whether the stomach has the metabolic capacity to account for first-pass metabolism. The aim of this study was to assess ethanol metabolism by human gastric mucosa cells in primary culture. METHODS: Cells were incubated with [1-14C]ethanol, and the quantity of ethanol oxidized was measured by the production of [1-14C]acetate. RESULTS: Gastric cells cultured from men produced 7.3 +/- 3.5 mumol acetate.10(6) cells-1.h-1, which was more than that generated in cells from women (3.2 +/- 0.6; P < 0.05). Acetate production was inhibited by 4-methylpyrazole (a class I alcohol dehydrogenase [ADH] inhibitor) and by m-nitrobenzaldehyde (a selective substrate for class IV ADH isoenzyme) but not by sodium azide (a catalase inhibitor). Cimetidine (a gastric ADH inhibitor) reduced acetate production by as much as 59%, whereas ranitidine had no significant effect. CONCLUSIONS: Human gastric cells metabolize sufficient alcohol to account for the bulk of first-pass metabolism. At least two isozymes of gastric ADH contribute to this metabolism. Cimetidine, but not ranitidine, inhibits gastric alcohol metabolism in keeping with its inhibition of in vivo first-pass metabolism.
Subject(s)
Ethanol/metabolism , Gastric Mucosa/metabolism , Acetic Acid/metabolism , Adult , Aged , Aged, 80 and over , Alcohol Dehydrogenase/physiology , Cells, Cultured , Female , Gastric Mucosa/cytology , Humans , Isoenzymes/physiology , Male , Middle AgedABSTRACT
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.
Subject(s)
Cimetidine/pharmacology , Ethanol/antagonists & inhibitors , Ethanol/metabolism , Gastric Mucosa/metabolism , Alcohol Dehydrogenase/antagonists & inhibitors , Alcohol Dehydrogenase/metabolism , Animals , Cells, Cultured , Gastric Mucosa/cytology , Male , Rats , Rats, Sprague-Dawley , Stomach/cytologyABSTRACT
An exceedingly rare tumor was found coincidentally in a young woman who had salpingectomy. The benign tumor was complex in nature and consisted of a lymphangioma and a well-encapsulated lipoma located in the mesentery of the small intestine. This tumor is compared with the similar ones mentioned so far in the literature.
