Cytochrome P4502E1 inducibility and hydroxyethyl radical formation among alcoholics
Cytochrome P4502E1 inducibility and hydroxyethyl radical formation among alcoholics
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DOI：
10.1016/s0168-8278(98)80279-1
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发表时间：
1998-04-01
影响因子：
25.7
通讯作者：
Albano, E
中科院分区：
文献类型：
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作者：
Dupont, I;Lucas, D;Albano, E
背景/目的：动物研究表明细胞色素 P4502E1 (CYP2E1) 的诱导可调节乙醇引起的氧化损伤。由于 CYP2E1 活性在人类中差异很大，我们研究了 CYP2E1 活性的差异是否可能影响酒精滥用者中羟乙基自由基的形成和脂质过氧化的刺激。方法：氯唑沙宗氧化（CYP2E1 活性指标）和抗体水平在 51 名酗酒者中研究了与羟乙基自由基和丙二醛蛋白加合物的反应。 结果：我们观察到 51 名酗酒者中的 40 名 (78%) 中，氯唑沙宗氧化高于对照水平，与乙醇诱导的 CYP2E1 一致。然而，在其余 22% 的患者中，尽管酒精摄入量相似，氯唑沙宗氧化仍在控制范围内，表明缺乏CYP2E1 诱导性。在没有 CYP2E1 诱导的受试者中，与羟乙基自由基蛋白加合物反应的 IgG 不存在，而在诱导 CYP2E1 活性的酗酒者中，与羟乙基自由基蛋白加合物反应的 IgG 显着增加，无论 CYP2E1 诱导能力如何，所有患者中抗丙二醛蛋白加合物的 IgG 均增加。此外，与酒精肝患者相比，在没有肝病临床和生化症状的酗酒者中，氯唑沙宗氧化显着降低结论：这些结果表明 CYP2E1 活性极大地影响人类羟乙基自由基的形成，并表明 CYP2E1 在酒精性肝病的发展中可能发挥作用。
Background/Aims: Animal studies have shown that the induction of cytochrome P4502E1 (CYP2E1) modulates oxidative damage induced by ethanol, Since CYP2E1 activity varies substantially in humans, we have investigated whether differences in CYP2E1 activity might influence the formation of hydroxyethyl free radicals and the stimulation of lipid peroxidation among alcohol abusers.Methods: Chlorzoxazone oxidation, an index of CYP2E1 activity, and the levels of antibodies reacting with hydroxyethyl radical and malonyldialdehyde protein adducts were investigated in 51 alcoholic patients.Results: We observed that in 40 out of 51 (78%) alcoholics, chlorzoxazone oxidation was increased over the control levels, consistently with CYP2E1 induction by ethanol, However, in the remaining 22% of the patients, in spite of a similar alcohol intake, chlorzoxazone oxidation was within the control range, indicating a lack of CYP2E1 inducibility. IgG reacting with hydroxyethyl free radical-protein adducts were absent in subjects without CYP2E1 induction, while they were significantly increased in alcoholics with induced CYP2E1 activity, IgG against malonyldialdehyde protein-adducts were increased in all patients, irrespective of CYP2E1 inducibility, Moreover, chlorzoxazone oxidation was significantly lower in alcoholics without clinical and biochemical signs of liver disease as compared to patients with alcoholic liver disease.Conclusions: These results indicate that CYP2E1 activity greatly influences the formation of hydroxyethyl radicals in humans, and suggest a possible role of CYP2E1 in the development of alcoholic liver disease.