DAIDZIN SUPPRESSES ETHANOL-CONSUMPTION BY SYRIAN GOLDEN-HAMSTERS WITHOUT BLOCKING ACETALDEHYDE METABOLISM
DAIDZIN SUPPRESSES ETHANOL-CONSUMPTION BY SYRIAN GOLDEN-HAMSTERS WITHOUT BLOCKING ACETALDEHYDE METABOLISM
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DOI：
10.1073/pnas.92.19.8990
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发表时间：
1995-09-12
影响因子：
11.1
通讯作者：
VALLEE, BL
中科院分区：
文献类型：
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作者：
KEUNG, WM;LAZO, O;VALLEE, BL
大豆苷是一种有效的、选择性的和可逆的人线粒体乙醛脱氢酶(ALDH)抑制剂，可以抑制叙利亚金黄地鼠自由选择的乙醇摄取。其他ALDH抑制剂，如双硫兰(Antabuse)和柠檬酸碳化钙(Temposl)，也被证明可以抑制实验动物的乙醇摄入，并被认为是通过抑制由摄入的乙醇产生的乙醛的代谢来发挥作用的。为了确定大豆苷是否抑制体内的乙醛代谢，在给予试验剂量的乙醇后，测定了大豆苷组仓鼠的血浆乙醛，大豆苷组每天150 mg/kg。6天)显著抑制(>；70%)仓鼠的乙醇摄入量，但不影响整体乙醛代谢。相比之下，在给予相同剂量的乙醇后，双硫兰组仓鼠的血浆乙醛浓度达到0.9 mM，是对照组的70倍。在体外，大豆苷对仓鼠肝线粒体催化的乙醛氧化有很强的抑制作用，其IC50值为0.4 mU M，大大低于大豆苷组地鼠肝线粒体的浓度(70 MU M)。这些结果表明，(I)大豆苷的作用不同于经典的、广效的ALDH抑制剂(如双硫胺)，以及(Ii)对大豆苷敏感的线粒体ALDH不是唯一对金黄地鼠乙醛代谢至关重要的酶。
Daidzin is a potent, selective, and reversible inhibitor of human mitochondrial aldehyde dehydrogenase (ALDH) that suppresses free-choice ethanol intake by Syrian golden hamsters. Other ALDH inhibitors, such as disulfiram (Antabuse) and calcium citrate carbimide (Temposil), have also been shown to suppress ethanol intake of laboratory animals and are thought to act by inhibiting the metabolism of acetaldehyde produced from ingested ethanol, To determine whether or not daidzin inhibits acetaldehyde metabolism in vivo, plasma acetaldehyde in daidzin-treated hamsters was measured after the administration of a test dose of ethanol, Daidzin treatment (150 mg/kg per day i.p. for 6 days) significantly suppresses (> 70%) hamster ethanol intake but does not affect overall acetaldehyde metabolism. In contrast, after administration of the same ethanol dose, plasma acetaldehyde concentration in disulfiram-treated hamsters reaches 0.9 mM, 70 times higher than that of the control. In vitro, daidzin suppresses hamster liver mitochondria-catalyzed acetaldehyde oxidation very potently with an IC50 value of 0.4 mu M, which is substantially lower than the daidzin concentration (70 mu M) found in the liver mitochondria of daidzin-treated hamsters. These results indicate that (i) the action of daidzin differs from that proposed for the classic, broad-acting ALDH inhibitors (e.g., disulfiram), and (ii) the daidzin-sensitive mitochondrial ALDH is not the one and only enzyme that is essential for acetaldehyde metabolism in golden hamsters.