Garlic compounds minimize intracellular oxidative stress and inhibit nuclear factor-κB activation
Garlic compounds minimize intracellular oxidative stress and inhibit nuclear factor-κB activation
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DOI：
10.1093/jn/131.3.1020s
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发表时间：
2001-03-01
影响因子：
4.2
通讯作者：
Lau, BHS
中科院分区：
文献类型：
--
作者：
Ide, N;Lau, BHS
低密度脂蛋白的氧化修饰在动脉粥样硬化的发生和发展中起着重要作用，本研究检测了老年大蒜提取物(AGE)及其主要化合物S-烯丙基半胱氨酸(SAC)对氧化低密度脂蛋白(Ox-LDL)诱导的内皮细胞(EC)损伤的影响，乳酸脱氢酶(LDH)的释放作为膜损伤的指标，四甲基偶氮唑蓝(MTT法)检测细胞存活率，硫代巴比妥酸反应物质(TBARS)检测脂质过氧化。氧化低密度脂蛋白导致乳酸脱氢酶释放增加，细胞活力丧失，泪液形成。年龄和SAC都阻止了所有这些变化。为阐明其作用机制，测定了AGE和SAC对EC细胞内谷胱甘肽(GSH)水平以及EC和巨噬细胞释放过氧化产物(M Phi)的影响。氧化低密度脂蛋白消耗细胞内GSH，增加过氧化产物的释放。AGE和SAC均抑制这些变化。检测SAC对过氧化氢(H_2O_2)或肿瘤坏死因子(TNF)-α诱导的核因子(NF)-kappaB活化的影响。用SAC预处理EC可抑制NF-kappaB的活化。我们证明AGE和SAC都可以通过阻止EC细胞内GSH耗竭和最大限度地减少EC和M phi释放的过氧化物质来保护EG免受Ox-LDL诱导的损伤。SAC还可抑制过氧化氢或肿瘤坏死因子-α诱导的核因子-kappaB的激活。我们的数据表明，AGE及其主要化合物SAG可能对预防动脉粥样硬化有用。
Oxidative modification of LDL has been recognized as playing an important role in the initiation and progression of atherosclerosis, In this study, we determined the effects of aged garlic extract (AGE) and its major compound, S-allylcysteine (SAC), on oxidized LDL (Ox-LDL)-induced injury in endothelial cells (EC), Lactate dehydrogenase (LDH) release as an index of membrane damage, methylthiazol tetrazoium (MTT) assay for cell viability and thiobarbituric acid reactive substances (TBARS) indicating lipid peroxidation were measured. Ox-LDL caused an increase of LDH release, loss of cell viability and TEARS formation. Both AGE and SAC prevented all of these changes. To elucidate the mechanism, effects of AGE or SAC on intracellular glutathione (GSH) level in EC, and release of peroxide from EC and macrophages (M Phi) were determined. Ox-LDL depleted intracellular GSH and increased release of peroxides. Both AGE and SAC inhibited these changes. Effects of SAC on hydrogen peroxide (H2O2) or tumor necrosis factor (TNF)-alpha -induced nuclear factor (NF)-kappaB activation were determined. Pretreatment of EC with SAC inhibited NF-kappaB activation. We demonstrated that both AGE and SAC can protect EG from Ox-LDL-induced injury by preventing intracellular GSH depletion in EC and by minimizing release of peroxides from EC and M Phi. SAC also inhibited H2O2- or TNF-alpha -induced NF-kappaB activation. Our data suggest that AGE and its main compound, SAG, may be useful for prevention of atherosclerosis.