Lapenna D, de Gioia S, Ciofani G, Bruno C, Porreca E, Pierdomenico S D, Cuccurullo F
Dipartimento di Medicina e Scienze dell'Invecchiamento, Università degli Studi G. d'Annunzio, Facoltà di Medicina e Chirurgia, Chieti, Italy.
FEBS Lett. 1998 Oct 9;436(3):357-60. doi: 10.1016/s0014-5793(98)01166-1.
We found that ticlopidine, at therapeutically relevant concentrations (2.5-10 microM), but not aspirin nor salicylate, significantly counteracted copper-driven human LDL oxidation. Ticlopidine, at 5 and 10 microM, was also antioxidant on peroxyl radical-induced LDL oxidation; yet it was ineffectual on thiol and ascorbate oxidation mediated by peroxyl radicals themselves, suggesting that drug antioxidant capacity is somehow related to the lipoprotein nature of the oxidizable substrate, but not to radical scavenging. The drug could not indeed react with the stable free radical 1,1-diphenyl-2-pycrylhydrazyl, nor had apparent metal complexing-inactivating activity. Thus, ticlopidine has antioxidant effects on LDL oxidation, which, together with its anti-platelet activity, could confer peculiar antiatherogenic properties to the drug in vivo.
我们发现,噻氯匹定在治疗相关浓度(2.5 - 10微摩尔)时,能显著对抗铜驱动的人低密度脂蛋白(LDL)氧化,而阿司匹林和水杨酸盐则无此作用。5微摩尔和10微摩尔的噻氯匹定对过氧自由基诱导的LDL氧化也具有抗氧化作用;然而,它对过氧自由基自身介导的硫醇和抗坏血酸氧化无效,这表明药物的抗氧化能力在某种程度上与可氧化底物的脂蛋白性质有关,而与自由基清除无关。该药物确实不能与稳定自由基1,1 - 二苯基 - 2 - 苦基肼反应,也没有明显的金属络合失活活性。因此,噻氯匹定对LDL氧化具有抗氧化作用,这与其抗血小板活性一起,可能使该药物在体内具有独特的抗动脉粥样硬化特性。