Inhibition of the microsomal oxidation of ethanol and 1-butanol by the free-radical, spin-trapping agent 5,5-dimethyl-1-pyrroline-1-oxide.

Inhibition of the microsomal oxidation of ethanol and 1-butanol by the free-radical, spin-trapping agent 5,5-dimethyl-1-pyrroline-1-oxide.
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自由基自旋捕获剂 5,5-二甲基-1-吡咯啉-1-氧化物抑制乙醇和 1-丁醇的微粒体氧化。

DOI:
10.1016/0003-9861(80)90049-1
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发表时间:
1980
影响因子:
3.9
通讯作者:
Cohen,G
Cohen,G
中科院分区:
生物学3区
文献类型:
--
作者:
Cederabum,AI;Cohen,G

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自由基、自旋捕获剂5,5-二甲基-1-吡咯啉-1-氧化物(DMPO)可抑制乙醇和1-丁醇的微粒体氧化以及2-酮基-4-硫代甲基丁酸酯的代谢。DMPO还阻断了由添加铁-EDTA到微粒体引起的乙醇氧化的刺激。先前其他人对DMPO的电子自旋共振研究表明,由大鼠肝微粒体产生并被EDTA铁增强的自由基是羟基自由基。在本研究中,DMPO对以NADPH为底物的微粒体耗氧量没有影响,对NADPH-细胞色素还原酶活性也没有影响,对氨基比林的去甲基化或苯胺的羟基化也没有影响。因此,排除了DMPO对微粒体的一般毒性作用。DMPO也未能抑制过氧化氢酶依赖性途径的乙醇氧化微粒体。使用Chelex 100树脂和螯合剂二亚乙基三胺五乙酸的实验排除了试剂中污染铁的任何主要作用。这些结果倾向于将负责乙醇、1-丁醇和2-酮基-4-硫代甲基丁酸的微粒体代谢的自由基鉴定为被DMPO捕获的自由基,即羟基自由基。
The free-radical, spin-trapping agent, 5,5-dimethyl-1-pyrroline-1-oxide (DMPO), inhibited the microsomal oxidation of ethanol and 1-butanol as well as the metabolism of 2-keto-4-thiomethylbutyrate. DMPO also blocked the stimulation of ethanol oxidation caused by the addition of iron-EDTA to microsomes. Previous electron spin resonance studies with DMPO by others had shown that the free radical produced by rat liver microsomes and augmented by iron-EDTA was the hydroxyl radical. In the current study, DMPO had no effect on microsomal oxygen consumption with NADPH as substrate, nor on NADPH-cytochromecreductase activity, nor on the demethylation of aminopyrine or the hydroxylation of aniline. Therefore, a general toxic action of DMPO on microsomes is excluded. DMPO also failed to inhibit the catalase-dependent pathway of ethanol oxidation by microsomes. Experiments with Chelex 100 resin and the chelating agent, diethylenetri-aminepentaacetic acid, rule out any major role for contaminating iron in the reagents. These results tend to identify the free radical responsible for microsomal metabolism of ethanol, 1-butanol, and 2-keto-4-thiomethylbutyrate as the radical trapped by DMPO, namely the hydroxyl radical.
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