Role of quinone reductase in in vivo ethanol metabolism and toxicity.
Role of quinone reductase in in vivo ethanol metabolism and toxicity.
复制标题
醌还原酶在体内乙醇代谢和毒性中的作用。
DOI：
10.1006/taap.1994.1015
复制
发表时间：
1994
影响因子：
3.8
通讯作者：
Rubin,RJ
中科院分区：
文献类型：
--
作者：
Chung,JH;Cha,YN;Rubin,RJ
醌还原酶（QR），在合适的底物存在下。导致NADH再生NAD+。为了验证QR可以在乙醇代谢和毒性中发挥作用的假设，我们研究了醌和诱导水平的QR对雄性大鼠和小鼠体内乙醇的影响。已知丁基羟基茴香醚（BHA）既能诱导QR，又能代谢为叔丁基醌（TBQ）。饲粮中添加BHA(0.75%，连续10 d)，再灌胃添加乙醇（4 g/ kg），可提高大鼠和小鼠血液乙醇的消失率，降低其曲线下面积（AUC）。此外，BHA预处理大鼠被证明可以防止乙醇诱导的24小时肝脏甘油三酯积累。此外，在大鼠中，TBQ （5 mg/kg, ip）导致AUC和肝脏甘油三酯积累降低，尽管乙醇消失率没有显著影响。在BHA喂养的大鼠中，TBQ对乙醇消失率和AUC的影响比单独处理TBQ或BHA更大。这些治疗方案都没有导致乙醇分布体积的显著变化。因此，这些结果支持了这样的假设，即QR的诱导和/或醌类药物的施用可以增强体内乙醇的代谢并降低肝毒性。
Quinone reductase (QR), in the presence of suitable substrate. results in the regeneration of NAD+from NADH. To test the hypothesis that QR can play a role in ethanol metabolism and toxicity, we studied the effect of a quinone as well as of induced levels of QR on ethanol administered in vivo to male rats and mice. Butylated hydroxyanisole (BHA) is known both to induce QR and to be metabolized to tert-butyl quinone (TBQ). Dietary BHA (0.75% for 10 days), followed by oral ethanol (4 g/ kg, by gavage), increased the rate of ethanol disappearance and decreased the area under the curve (AUC) for blood ethanol in both rats and mice. In addition, BHA pretreatment of rats was shown to prevent ethanol-induced 24-hr hepatic triglyceride accumulation. Also, in rats, TBQ (5 mg/kg, ip) led to decreased AUC and hepatic triglyceride accumulation, although the ethanol disappearance rate was not significantly affected. TBQ in BHA-fed rats resulted in even greater effects on the ethanol disappearance rate and AUC than TBQ or BHA treatment alone. None of these treatment regimens resulted in a significant change in volume of distribution of ethanol. Thus, these results support the hypothesis that induction of QR and/or administration of quinones leads to enhanced in vivo metabolism of ethanol and decreased hepatotoxicity.