Mirmiran-Yazdy S A, Haber P S, Korsten M A, Mak K M, Gentry R T, Batra S C, Lieber C S
Alcohol Research and Treatment Center, Veterans Affairs Medical Center, Bronx, New York.
Gastroenterology. 1995 Mar;108(3):737-42. doi: 10.1016/0016-5085(95)90446-8.
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.
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.
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.
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.
背景/目的:多项研究表明,胃具有足够的乙醇脱氢酶活性来代谢大量酒精,且西咪替丁会抑制这种乙醇脱氢酶活性。然而,乙醇的胃代谢及其被西咪替丁抑制的情况仍存在争议。鉴于体内评估乙醇胃代谢存在困难,故在体外对此进行了研究。
将培养的大鼠胃上皮细胞与200 mmol/L [1-¹⁴C]乙醇一起孵育90分钟,分别加入或不加入西咪替丁(0.1 - 1 mmol/L)或奥美拉唑(1 mmol/L)。通过离子交换色谱法测定产生的乙酸量来测量胃细胞氧化的乙醇量。
汇合状态下的大多数细胞具有黏液细胞的典型特征。胃细胞代谢了大量乙醇,足以解释大鼠体内乙醇的首过代谢。西咪替丁而非奥美拉唑使乙醇代谢降低了39.9% ± 4.9%(P < 0.01),这种抑制作用与先前报道的体内首过代谢的抑制作用相当。
组织培养中的胃细胞能够显著氧化乙醇,体外氧化速率足以解释体内乙醇的首过代谢,且西咪替丁在组织培养中抑制乙醇代谢,这一作用与其在体内降低首过代谢的作用相似。