DECREASE IN CYTOCHROME P4502E1 AS ASSESSED BY THE RATE OF CHLORZOXAZONE HYDROXYLATION IN ALCOHOLICS DURING THE WITHDRAWAL PHASE
DECREASE IN CYTOCHROME P4502E1 AS ASSESSED BY THE RATE OF CHLORZOXAZONE HYDROXYLATION IN ALCOHOLICS DURING THE WITHDRAWAL PHASE
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DOI：
10.1111/j.1530-0277.1995.tb01516.x
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发表时间：
1995-04-01
影响因子：
3.2
通讯作者：
MENEZ, JF
中科院分区：
文献类型：
--
作者：
LUCAS, D;MENEZ, C;MENEZ, JF
为了评估酒精中毒者细胞色素P4502 E1（CYP 2 E1）的诱导作用，采用HPLC法测定了6-羟基氯唑沙宗（6-OH-CHZ）和氯唑沙宗（CHZ）摄入后小时血液中CHZ浓度的比值。在对照组和酒精中毒患者停药1、2、3、4、5、8和21天后测定该比率。在酒精戒断后的2天内，发现30名对照者的该值为0.34 +/- 0.03，41名酒精中毒患者的该值为1.05 +/- 0.14。该比值在戒断期间迅速下降，如CYP 2 E1的短半衰期所证明的，发现其为2.5天。在戒酒8天或21天后检测CHZ代谢的患者显示与对照组相同的比值[分别为0.35 +/- 0.03（n = 28）和0.31 +/- 0.03（n = 34）]。γ-谷氨酰转移酶、碳水化合物缺乏转铁蛋白值、每日饮酒量和6-OH-CHZ/CHZ比值之间未观察到相关性。吸烟对CHZ羟基化速率没有影响，因为吸烟者与非吸烟者的比率相同[分别为0.33 +/- 0.025（n = 62）和0.33 +/- 0.02（n = 30）]。CHZ羟基化比率似乎是人体肝脏和肝外CYP 2 E1活性的良好反映。
To evaluate cytochrome P4502E1 (CYP2E1) induction in alcoholics, the ratio of the concentrations of 6-hydroxychlorzoxazone (6-OH-CHZ) and chlorzoxazone (CHZ) was measured in blood hr after CHZ ingestion using a HPLC method. This ratio was determined in controls and in alcoholic patients after 1, 2, 3, 4, 5, 8, and 21 days withdrawal. it was found to be 0.34 +/- 0.03 in 30 controls and 1.05 +/- 0.14 in 41 alcoholic patients within 2 days following ethanol withdrawal. This ratio decreased rapidly during withdrawal as attested by the short half-life of CYP2E1, which was found to be 2.5 days, Patients tested for CHZ metabolism after 8 or 21 days alcohol abstinence displayed the same ratio as controls [0.35 +/- 0.03 (n = 28) and 0.31 +/- 0.03 (n = 34), respectively]. No correlation was observed between gamma-glutamyltransferase, carbohydrate-deficient transferrin values, the amount of alcohol consumed/day, and the 6-OH-CHZ/CHZ ratio. There was no influence of smoking on the rate of CHZ hydroxylation, because smokers displayed the same ratio as nonsmokers [0.33 +/- 0.025 (n = 62) and 0.33 +/- 0.02 (n = 30), respectively]. The CHZ hydroxylation ratio seems to be a good reflection of the hepatic and extrahepatic CYP2E1 activity in humans.