GENERATION OF FREE-RADICAL INTERMEDIATES FROM FOREIGN COMPOUNDS BY NEUTROPHIL-DERIVED OXIDANTS
GENERATION OF FREE-RADICAL INTERMEDIATES FROM FOREIGN COMPOUNDS BY NEUTROPHIL-DERIVED OXIDANTS
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DOI：
10.1172/jci111868
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发表时间：
1985-01-01
影响因子：
15.9
通讯作者：
SOHNLE, PG
中科院分区：
文献类型：
--
作者：
KALYANARAMAN, B;SOHNLE, PG
大量的外来化合物，包括许多药物、工业污染物和环境化学品，可以在适当的条件下被氧化成潜在有毒的自由基中间体。评价了由嗜中性粒细胞髓过氧化物酶系统产生的氧化剂从几种这样的化合物产生自由基中间体的能力。由人外周血中性粒细胞产生的次氯酸钠或次氯酸以牛磺酸氯胺的形式被捕获，都被发现能够从氯丙嗪、氨基比林和苯肼产生自由基。这些自由基中间体被证明是由可见光光谱和直接ESR（氯丙嗪和氨基比林自由基）或自旋捕获（从苯肼产生的苯基自由基）。由嗜中性粒细胞产生的稳定氧化剂（即，在没有添加牛磺酸的情况下，存在于刺激的嗜中性粒细胞的上清液中的那些）也被发现能够产生自由基中间体。氧化剂的产生和中性粒细胞上清液产生这些自由基的能力几乎完全消除了叠氮化钠，髓过氧化物酶抑制剂。某些化合物被中性粒细胞氧化成具有潜在破坏性的亲电自由基形式可能代表了这些物质的新代谢途径，并且在药物毒性和化学致癌过程中可能很重要。
A large number of foreign compounds, including many drugs, industrial pollutants and environmental chemicals, can be oxidized under appropriate conditions to potentially toxic free radical intermediates. The ability of the oxidants produced by the neutrophil myeloperoxidase system to generate free radical intermediates from several such compounds was evaluated. Sodum hypochlorite or hypochlorous acid produced by human peripheral blood neutrophils and trapped in the form of taurine chloramine were both found to be capable of producing free radicals from chlorpromazine, aminopyrine and phenylhydrazine. These radical intermediates were demonstrated by visible light spectroscopy and by direct ESR (for the chlorpromazine and aminopyrine radicals) or by spin-trapping (for the phenyl radical generated from phenylhydrazine). Stable oxidants produced by the neutrophils (i.e., those present in the supernatants of stimulated neutrophils in the absence of added taurine) also were found to be capable of generating free radical intermediates. The production of the oxidants and the ability of neutrophil supernatants to generate these radicals were almost completely eliminated by sodium azide, a myeloperoxidase inhibitor. The oxidation by neutrophils of certain chemical compounds to potentially damaging electrophilic free radical forms may represent a new metabolic pathway for these substances and could be important in the processes of drug toxicity and chemical carcinogenesis.