Ueshima Y, Takase S, Takada A
Department of Internal Medicine, Kanazawa Medical University, Ishikawa, Japan.
Gastroenterol Jpn. 1990 Dec;25(6):708-14. doi: 10.1007/BF02779184.
In this study the authors analyzed ethanol (Et-OH) and acetaldehyde (Ac-CHO) metabolism in cultured hepatocytes isolated from chronic alcoholic rats. Hepatocytes were isolated and cultured from two groups of rats, one was fed with a liquid diet containing Et-OH and another was pair-fed with a control diet for 4 weeks. After 48 hours of the primary culture, Et-OH was added to the culture medium at a final concentration of 5 mM with or without 2 mM 4-methyl pyrazole (Py). Serial changes of Et-OH and Ac-CHO levels in the medium for 48 hours were determined in 4 groups of the alcohol alone, alcohol-Py, control and control-Py groups. In the alcohol alone and control groups, Et-OH disappearance rates (EDR), which are roughly equivalent to Et-OH oxidation rates in the hepatocytes, were significantly higher than those in the corresponding Py treated groups. In the two alcoholic groups, the EDR was significantly higher than those in the corresponding control groups. In cultured hepatocytes, 75-80% of Ac-CHO produced from Et-OH was oxidized. The increasing rates of Ac-CHO (AcICR), a function of Ac-CHO production and oxidation rates in the hepatocytes, increased in parallel with the increase in the EDR. However, the AcICR/EDR rate, which is a parameter of the Ac-CHO oxidation rate in the hepatocytes, was not different among the 4 groups. These results indicate that the cultured cells maintain the characteristics of Et-OH metabolism in chronic alcoholic rats and may also be used for the study of Et-OH and Ac-CHO metabolism as an in vitro model.
在本研究中,作者分析了从慢性酒精中毒大鼠分离的培养肝细胞中乙醇(Et-OH)和乙醛(Ac-CHO)的代谢情况。从两组大鼠中分离并培养肝细胞,一组喂食含Et-OH的液体饲料,另一组与对照饲料配对喂养4周。原代培养48小时后,在有或无2 mM 4-甲基吡唑(Py)的情况下,将Et-OH以终浓度5 mM添加到培养基中。在单独乙醇、乙醇-Py、对照和对照-Py这4组中,测定培养基中48小时内Et-OH和Ac-CHO水平的系列变化。在单独乙醇组和对照组中,大致等同于肝细胞中Et-OH氧化速率的Et-OH消失率(EDR)显著高于相应Py处理组。在两个酒精组中,EDR显著高于相应对照组。在培养的肝细胞中,由Et-OH产生的Ac-CHO的75-80%被氧化。Ac-CHO增加率(AcICR)是肝细胞中Ac-CHO产生和氧化速率的函数,与EDR的增加平行增加。然而,作为肝细胞中Ac-CHO氧化速率参数的AcICR/EDR率在4组之间没有差异。这些结果表明,培养的细胞保持了慢性酒精中毒大鼠中Et-OH代谢的特征,也可作为体外模型用于研究Et-OH和Ac-CHO的代谢。