Ide N, Lau B H
Department of Microbiology and Molecular Genetics, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA.
J Nutr. 2001 Mar;131(3s):1020S-6S. doi: 10.1093/jn/131.3.1020S.
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 TBARS 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 (H(2)O(2)) or tumor necrosis factor (TNF)-alpha-induced nuclear factor (NF)-kappa B activation were determined. Pretreatment of EC with SAC inhibited NF-kappa B activation. We demonstrated that both AGE and SAC can protect EC 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 H(2)O(2)- or TNF-alpha-induced NF-kappa B activation. Our data suggest that AGE and its main compound, SAC, may be useful for prevention of atherosclerosis.
低密度脂蛋白（LDL）的氧化修饰已被认为在动脉粥样硬化的发生和发展中起重要作用。在本研究中，我们测定了 aged garlic extract（AGE）及其主要成分 S -烯丙基半胱氨酸（SAC）对氧化型 LDL（Ox - LDL）诱导的内皮细胞（EC）损伤的影响。测定了作为膜损伤指标的乳酸脱氢酶（LDH）释放、用于评估细胞活力的甲基噻唑四氮唑（MTT）法以及指示脂质过氧化的硫代巴比妥酸反应性物质（TBARS）。Ox - LDL 导致 LDH 释放增加、细胞活力丧失和 TBARS 形成。AGE 和 SAC 均可防止所有这些变化。为阐明其机制，测定了 AGE 或 SAC 对 EC 细胞内谷胱甘肽（GSH）水平以及 EC 和巨噬细胞（M Phi）中过氧化物释放的影响。Ox - LDL 消耗细胞内 GSH 并增加过氧化物释放。AGE 和 SAC 均抑制这些变化。测定了 SAC 对过氧化氢（H₂O₂）或肿瘤坏死因子（TNF）-α诱导的核因子（NF）-κB 激活的影响。用 SAC 预处理 EC 可抑制 NF -κB 激活。我们证明，AGE 和 SAC 均可通过防止 EC 细胞内 GSH 耗竭以及使 EC 和 M Phi 中的过氧化物释放降至最低来保护 EC 免受 Ox - LDL 诱导的损伤。SAC 还抑制 H₂O₂或 TNF -α诱导的 NF -κB 激活。我们的数据表明，AGE 及其主要成分 SAC 可能对预防动脉粥样硬化有用。
