A NOVEL BIOLOGICALLY-ACTIVE SELENO-ORGANIC COMPOUND .5. INHIBITION BY EBSELEN (PZ-51) OF RAT PERITONEAL NEUTROPHIL LIPOXYGENASE
A NOVEL BIOLOGICALLY-ACTIVE SELENO-ORGANIC COMPOUND .5. INHIBITION BY EBSELEN (PZ-51) OF RAT PERITONEAL NEUTROPHIL LIPOXYGENASE
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DOI：
10.1016/0006-2952(85)90569-6
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发表时间：
1985-01-01
影响因子：
5.8
通讯作者：
WENDEL, A
中科院分区：
文献类型：
--
作者：
SAFAYHI, H;TIEGS, G;WENDEL, A
用Ca和离子载体刺激糖原诱导的大鼠腹膜PMNL（多形核白细胞）悬浮液，内源性花生四烯酸产生白三烯。研究了无毒、抗炎的有机硒化合物艾布selen （pz51）的作用。当用高效液相色谱法分析受刺激细胞培养基的乙醇提取物时，发现依布selen对LTB4[白三烯B4]形成的抑制作用呈剂量依赖性，同时减少了5-羟基二碳四烯酸[5-羟基四烯酸]的产生。在20 .mu处观察到半最大抑制。/ 1 ebselen摩尔数。在使用不同的高效液相色谱系统对细胞和培养基的氯仿提取物进行分析后，得到了类似的发现。在这些条件下，当纯化的谷胱甘肽过氧化物酶+谷胱甘肽存在时，5-HETE的形成增强与LTB4和其他二羟基二十碳四烯酸异构体的产生减少有关。报道的埃布硒的GSH过氧化物酶样活性，催化5-HPETE[5-羟基过氧化物-二十碳四烯酸]还原为5-HETE，不能解释这一发现。脂氧合酶反应本身显然代表了依布硒抑制LTB4形成的位点。
Suspensions of rat peritoneal PMNL [polymorphonuclear leukocyte] elicited with glycogen were stimulated by Ca and an ionophore to produce leukotrienes from endogenous arachidonic acid. The effect of the non-toxic, anti-inflammatory seleno-organic compound, ebselen (PZ 51) was investigated. When ethanolic extracts of the medium of stimulated cells were analyzed by HPLC [high performance liquid chromatography] a dose-dependent inhibition by ebselen of LTB4 [leukotriene B4] formation with a concomitant decrease of 5-HETE [5-hydroxy-eicosa-tetraenoic acid] production was found. Half-maximum inhibition was observed at 20 .mu.moles/1 ebselen. Similar findings were obtained after analysis of chloroform extracts of both cells and medium using a different HPLC system. Under these conditions, enhanced 5-HETE formation was associated with reduced production of LTB4 and other di-HETE [dihydroxy-eicosa-tetraenoic acid] isomers, when purified glutathione peroxidase + GSH were present. The reported GSH peroxidase-like activity of ebselen, catalyzing the reduction of 5-HPETE [5-hydroperoxy-eicosa-tetraenoic acid] to 5-HETE, can not account for the findings. The lipoxygenase reaction itself apparently represents the site of inhibition of LTB4 formation by ebselen.