乙醇对大鼠肝脏和结肠中视黄醇氧化的抑制作用。
Inhibition of retinol oxidation by ethanol in the rat liver and colon.
作者信息
Parlesak A, Menzl I, Feuchter A, Bode J C, Bode C
机构信息
Hohenheim University (140), Department of Physiology of Nutrition, Garbenstr. 28, D-70599 Stuttgart, Germany.
出版信息
Gut. 2000 Dec;47(6):825-31. doi: 10.1136/gut.47.6.825.
BACKGROUND
Epidemiological evidence has been presented for an increased risk of development of colon cancer after chronic alcohol abuse. Alcohol is degraded by cytosolic alcohol dehydrogenases that also are capable of retinol oxidation. Inhibition of retinol oxidation to retinoic acid has been shown to occur in parallel with profound impairment of intracellular retinoid signal transduction and loss of cell differentiation control.
AIMS
In the present study, the change in cytosolic retinol oxidation and retinoic acid formation by ethanol concentrations that occur in body tissues in humans after social drinking was measured in cells from the liver, and small and large intestine of the rat.
RESULTS
The specific catalytic efficiency V(max)/K(m) (ml/min/g) of cytosolic retinol oxidation in the large intestine (28.9) was found to be distinctly higher than that in the liver (3.4), while the efficiency in the small intestine was negligible (0.20). In the presence of increasing ethanol concentrations (9, 17, and 34 mM), V(max)/K(m) for retinol oxidation decreased in a dose dependent manner to 7.8% of the initial value in the large intestine and to 12% in the liver. The V(max)/K(m) of retinoic acid formation in the liver cytosol decreased to 15%.
CONCLUSIONS
Our data demonstrate impairment of hepatic and intestinal cytosolic retinol oxidation and retinoic acid formation by ethanol at concentrations in body tissues after social drinking in humans. The results suggest that the increased risk of developing colorectal neoplasias after alcohol abuse may, at least in part, be caused by impaired retinoid signal transduction.
背景
已有流行病学证据表明，长期酗酒会增加患结肠癌的风险。酒精由胞质乙醇脱氢酶降解，该酶也能够氧化视黄醇。研究表明，视黄醇氧化为视黄酸的过程受到抑制，同时细胞内类视黄醇信号转导严重受损，细胞分化控制丧失。
目的
在本研究中，测量了社交饮酒后人体组织中出现的乙醇浓度对大鼠肝脏、小肠和大肠细胞中胞质视黄醇氧化和视黄酸形成的影响。
结果
发现大肠中胞质视黄醇氧化的比催化效率V(max)/K(m)（毫升/分钟/克）（28.9）明显高于肝脏（3.4），而小肠中的效率可忽略不计（0.20）。在乙醇浓度增加（9、17和34 mM）的情况下，视黄醇氧化的V(max)/K(m)以剂量依赖方式降低，在大肠中降至初始值的7.8%，在肝脏中降至12%。肝脏胞质中视黄酸形成的V(max)/K(m)降至15%。
结论
我们的数据表明，社交饮酒后人体组织中乙醇浓度会损害肝脏和肠道胞质中的视黄醇氧化及视黄酸形成。结果表明，酗酒后患结直肠癌的风险增加可能至少部分是由类视黄醇信号转导受损引起的。
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