Flavin-dependent antioxidant properties of a new series of meso-N,N′-dialkyl-imidazolium substituted manganese(III) porphyrins
Flavin-dependent antioxidant properties of a new series of meso-N,N′-dialkyl-imidazolium substituted manganese(III) porphyrins
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DOI：
10.1016/j.bcp.2003.08.036
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发表时间：
2004-01-01
影响因子：
5.8
通讯作者：
Day, BJ
中科院分区：
文献类型：
--
作者：
Kachadourian, R;Johnson, CA;Day, BJ
许多人工合成的锰络合物在体外和体内都表现出催化抗氧化活性。这项研究报告了一系列新的中-N，N‘-二烷基咪唑取代的锰(III)卟啉的抗氧化能力，部分依赖于它们与内源性黄素依赖的氧化还原酶进行氧化还原循环的能力。用大鼠脑匀浆作为脂质来源和内源性氧化还原酶，比较了这些新型阳离子卟啉对脂质过氧化的抑制作用。以铁和抗坏血酸为脂质过氧化的引发剂，测定了两种脂质过氧化指标(硫代巴比妥酸活性物种(TBARS)和F-2-异前列烷)。所有中位-N，N‘-二烷基咪唑取代的卟啉都是有效的脂质过氧化抑制剂，其IC50在0.1~34um之间，其金属效应为：Mn(III)&Gt；Co(III)&Gt；Zn(II)。在脂质过氧化模型中，二苯基十二烷基氯化铵(DPI，一种黄素酶抑制剂)能够降低锰-卟啉的效力，并且锰-卟啉能促进大鼠脑匀浆中NADPH的氧化，这支持了黄素依赖的氧化还原酶抗氧化过程。这些数据表明，金属卟啉可能由于黄素依赖的氧化还原酶的存在或不存在而在组织中具有不同的抗氧化效果。(C)2003 Elsevier Inc.保留所有权利。
A number of synthetic manganese complexes exhibit both in vitro and in vivo catalytic antioxidant activities. This study reports that the antioxidant potencies of a new series of meso-N,N'-dialkyl-imidazolium substituted manganese(III) porphyrins are dependent, in part, on their ability to redox cycle with endogenous flavin-dependent oxidoreductases. Inhibition of lipid peroxidation activities of these novel cationic porphyrins was compared using rat brain homogenate as a source of lipids and endogenous oxidoreductases. Iron and ascorbate was used as initiators of lipid peroxidation, and two indices of lipid peroxidation (thiobarbituric acid reactive species (TBARS) and F-2-isoprostanes) were determined. All meso-N,N'-dialkyl-imidazolium substituted porphyrins tested were potent inhibitors of lipid peroxidation with IC50 ranging from 0.1 to 34 muM with a metal-dependent potency of Mn (III) > Co (III) > Zn (II). A flavin-dependent oxidoreductase antioxidant process was supported by the ability of the diphenyleneiodonium chloride (DPI, a flavoenzyme inhibitor) to decrease the potency of Mn-porphyrins in the lipid peroxidation model and that Mn-porphyrins stimulate NADPH oxidation in rat brain homogenates. These data suggest that metalloporphyrins may have differential antioxidant effects in tissues due to the presence or absence of flavin-dependent oxidoreductases. (C) 2003 Elsevier Inc. All rights reserved.