Pekoe G, Van Dyke K, Mengoli H, Peden D, English D
Agents Actions. 1982 Apr;12(1-2):232-8. doi: 10.1007/BF01965152.
The interaction of myeloperoxidase (MPO) with H2O2 and Cl- provides a potent antimicrobial/cytotoxic system for polymorphonuclear leukocytes (PMNs). MPO-related cytotoxicity may be associated with the formation of toxic oxidant MPO intermediates, HOCl, or both. MPO itself is able to oxidize drugs and cellular components. Non-steroidal anti-inflammatory drugs (NSAIDs) able to act as antioxidant free radical scavengers have recently been shown to inhibit luminol-enhanced chemiluminescence (CL) which results from the MPO-H2O2-Cl- reaction. CL is a measure of the activity of this reaction. At that time it was not clear whether the source of CL which these NSAIDs affected was HOCl or components of the initial MPO-H2O2-Cl- reaction. A NSAID antioxidant mechanism could affect MPO oxidant intermediates and HOCl. This study compares the effects of antioxidant NSAIDs, methylprednisone and free radical scavengers against MPO-based and NaOCl-based luminol-enhanced CL. Most NSAIDs which affected both MPO and NaOCl-CL appeared to share similar mechanisms, suggesting that MPO oxidant intermediates and HOCl are susceptible to NSAID effects. However, most NSAIDs were more effective against MPO-CL. The effect of these NSAIDs against MPO-CL followed the profile of NSAIDs effective in previous studies against PMN-CL. One exception to this was methylprednisone, which has no effect on PMN or MPO-CL, yet inhibited NaOCl-CL. This and other data suggest that MPO and not HOCl-related reactions are a major source of PMN-CL. Less effective NSAIDs affected NaOCl-CL better than MPO-CL. While both HOCl and MPO oxidant intermediates may be affected by NSAIDs, it appears that MPO oxidant intermediates or MPO itself are the primary target for NSAID antioxidant free radical scavenging mechanisms. These antioxidant effects impair the major killing system of the PMN and may be NSAIDs' primary anti-inflammatory mechanism. Although our data suggests the production of superoxide anion and hydroxyl radical from the MPO-H2O2-Cl- reaction, the actual presence or involvement of these free radical species is not confirmed herein.
髓过氧化物酶（MPO）与过氧化氢（H2O2）和氯离子（Cl-）的相互作用为多形核白细胞（PMN）提供了一种强大的抗菌/细胞毒性系统。MPO相关的细胞毒性可能与有毒的氧化型MPO中间体、次氯酸（HOCl）的形成或两者都有关。MPO本身能够氧化药物和细胞成分。最近发现，能够作为抗氧化自由基清除剂的非甾体抗炎药（NSAIDs）可抑制由MPO-H2O2-Cl-反应产生的鲁米诺增强化学发光（CL）。CL是该反应活性的一种度量。当时尚不清楚这些NSAIDs所影响的CL来源是HOCl还是初始MPO-H2O2-Cl-反应的成分。一种NSAID抗氧化机制可能会影响MPO氧化型中间体和HOCl。本研究比较了抗氧化NSAIDs、甲基泼尼松和自由基清除剂对基于MPO和基于次氯酸钠（NaOCl）的鲁米诺增强CL的影响。大多数同时影响MPO和NaOCl-CL的NSAIDs似乎具有相似的机制，这表明MPO氧化型中间体和HOCl易受NSAIDs的影响。然而，大多数NSAIDs对MPO-CL的作用更有效。这些NSAIDs对MPO-CL的作用与先前研究中对PMN-CL有效的NSAIDs的情况相符。其中一个例外是甲基泼尼松，它对PMN或MPO-CL无作用，但可抑制NaOCl-CL。这一发现及其他数据表明，MPO而非与HOCl相关的反应是PMN-CL的主要来源。效果较差的NSAIDs对NaOCl-CL的影响比对MPO-CL的影响更好。虽然HOCl和MPO氧化型中间体可能都受到NSAIDs的影响，但似乎MPO氧化型中间体或MPO本身是NSAID抗氧化自由基清除机制的主要靶点。这些抗氧化作用损害了PMN的主要杀伤系统，可能是NSAIDs的主要抗炎机制。尽管我们的数据表明MPO-H2O2-Cl-反应会产生超氧阴离子和羟基自由基，但本文未证实这些自由基的实际存在或参与情况。
