铁螯合剂去铁胺和1-烷基-2-甲基-3-羟基吡啶-4-酮在体外可抑制血管前列环素的合成。
The iron chelators desferrioxamine and 1-alkyl-2-methyl-3-hydroxypyrid-4-ones inhibit vascular prostacyclin synthesis in vitro.
作者信息
Jeremy J Y, Kontoghiorghes G J, Hoffbrand A V, Dandona P
机构信息
Department of Chemical Pathology and Human Metabolism, Royal Free Hospital and School of Medicine, London, U.K.
出版信息
Biochem J. 1988 Aug 15;254(1):239-44. doi: 10.1042/bj2540239.
Abstract
The iron chelators desferrioxamine (DFO), 1,2-dimethyl(L1)-, 1-ethyl-2-methyl(L1NEt)- and 1-propyl-2-methyl(L1NPr)-3-hydroxypyrid-4-ones inhibited rat aortic prostacyclin (PGI2) synthesis in vitro (rank order of potency: DFO greater than L1 greater than L1NEt greater than L1NPr) when stimulated with adrenaline, arachidonate and the Ca2+ ionophore A23187. The inhibitory action of the chelators was blocked by Fe3+ and Al3+ and reversed by washing and H2O2, but not by ascorbate. These data suggest that iron chelators inhibit prostanoid synthesis in intact tissue through the removal or binding of Fe3+ linked to cyclo-oxygenase. These iron chelators may be of therapeutic value in the treatment of inflammatory and other diseases via two mechanisms: (1) the inhibition of pro-inflammatory prostanoid synthesis and (2) the inhibition of toxic-free-radical generation by cyclo-oxygenase.
摘要
当用肾上腺素、花生四烯酸和钙离子载体A23187刺激时，铁螯合剂去铁胺（DFO）、1,2-二甲基（L1）、1-乙基-2-甲基（L1NEt）和1-丙基-2-甲基（L1NPr）-3-羟基吡啶-4-酮在体外抑制大鼠主动脉前列环素（PGI2）的合成（效力排序：DFO＞L1＞L1NEt＞L1NPr）。螯合剂的抑制作用被Fe3+和Al3+阻断，通过洗涤和H2O2可逆转，但抗坏血酸不能逆转。这些数据表明，铁螯合剂通过去除或结合与环氧化酶相连的Fe3+来抑制完整组织中前列腺素的合成。这些铁螯合剂可能通过两种机制在炎症和其他疾病的治疗中具有治疗价值：（1）抑制促炎性前列腺素的合成；（2）抑制环氧化酶产生有毒自由基。
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