A SERIES OF PROSTAGLANDIN-F2-LIKE COMPOUNDS ARE PRODUCED INVIVO IN HUMANS BY A NONCYCLOOXYGENASE, FREE RADICAL-CATALYZED MECHANISM
A SERIES OF PROSTAGLANDIN-F2-LIKE COMPOUNDS ARE PRODUCED INVIVO IN HUMANS BY A NONCYCLOOXYGENASE, FREE RADICAL-CATALYZED MECHANISM
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DOI：
10.1073/pnas.87.23.9383
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发表时间：
1990-12-01
影响因子：
11.1
通讯作者：
ROBERTS, LJ
中科院分区：
文献类型：
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作者：
MORROW, JD;HILL, KE;ROBERTS, LJ
越来越多的注意力集中在自由基在各种疾病的病理生理中的作用。自由基诱导的损伤的一个公认的目标是脂质过氧化。使用多种方法，我们发现一系列前列腺素f2样化合物在体内通过非环加氧酶机制产生，涉及自由基催化花生四烯酸的过氧化。这些化合物在正常人血浆和尿液中的含量分别为肌酐5 - 40pg /ml和500 - 4000pg /mg。在大鼠中，发现它们的形成增加了200倍，这与给药CCl4和diquat诱导的明显的自由基催化脂质过氧化有关。为了探讨这些类前列腺素是否能发挥生物活性，研究其中一种由这种机制形成的化合物8-epi-前列腺素f2 . α的作用。在大鼠肾脏中检测。8-epi-前列腺素F2.alpha输注。进入外周静脉(5。G /kg / min)或静脉注射（0.5-2.0 .mu）。G /kg / min)导致肾血流量和肾小球滤过率显著降低。这些前列腺素的形成是由自由基催化的，它们可以发挥强大的生物活性，这表明这些前列腺素可能作为病理生理介质参与氧化损伤。这些化合物的定量也可以提供一种非侵入性的方法来评估人体的氧化状态。这些类前列腺素的形成独立于环氧化酶的催化活性，这表明有时使用环氧化酶抑制剂来评估前列腺素在某些病理生理过程中的作用的可靠性可能存在局限性。
Increasing attention has focused on the role of free radicals derived from oxygen in the pathophysiology of a wide variety of disorders. One of the well-recognized targets of free radical-induced injury is peroxidation of lipids. Using a variety of approaches, we have found that a series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase mechanism involving free radical-catalyzed peroxidation of arachidonic acid. Levels of these compounds in normal human plasma and urine range from 5 to 40 pg/ml and 500 to 4000 pg/mg of creatinine, respectively. In rats, their formation was found to increase as much as 200-fold in association with marked free radical-catalyzed lipid peroxidation induced by administration of CCl4 and diquat. To explore whether these prostanoids can exert biological activity, the effects of one of the compounds formed by this mechanism, 8-epi-prostaglandin F2.alpha., was examined in the kidney in the rat. Infusion of 8-epi-prostaglandin F2.alpha. into a peripheral vein (5 .mu.g/kg per min) or intrarenally (0.5-2.0 .mu.g/kg per min) resulted in marked parallel reductions in renal blood flow and glomerular filtration rate. That the formation of these prostanoids is catalyzed by free radicals and that they can exert potent biological activity suggest that these prostanoids may participate as pathophysiological mediators in oxidant injury. Quantification of these compounds may also provide a noninvasive approach to assess oxidant status in humans. That the formation of these prostanoids occurs independent of the catalytic activity of the cyclooxygenase enzyme suggests that there may be limitations at times regarding the reliability of the use of cyclooxygenase inhibitors to assess the role of prostaglandins in certain pathophysiological processes.