Protective effect of photodegradation product of nifedipine against tumor necrosis factor alpha-induced oxidative stress in human glomerular endothelial cells
Protective effect of photodegradation product of nifedipine against tumor necrosis factor alpha-induced oxidative stress in human glomerular endothelial cells
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DOI：
10.2152/jmi.58.118
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发表时间：
2011-02-01
影响因子：
0.7
通讯作者：
Tamaki, Toshiaki
中科院分区：
文献类型：
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作者：
Fukuhara, Yayoi;Tsuchiya, Koichiro;Tamaki, Toshiaki
最近，越来越多的证据表明，抗高血压药物硝苯地平作为一种保护剂的内皮细胞，并认为该活动与其钙通道阻滞无关。硝苯地平是硝苯地平经代谢和光化学作用产生的一种代谢产物，由于硝苯地平不具有降压作用而被认为是硝苯地平的污染物。肿瘤坏死因子-α（TNF-α）处理抑制人肾小球内皮细胞（HGECs）的细胞活力并促进细胞间粘附分子1（ICAM-1）的表达，而NO-NIF预处理可显著恢复TNF-α诱导的细胞损伤，其程度与Trolox-C相同，并以浓度依赖性方式抑制ICAM-1的表达。此外，NO-NIF抑制过氧化氢枯烯诱导的细胞毒性，其通过氧化应激阻碍细胞膜的完整性，与Trolox-c一样有效。这些数据表明，NO-NIF是一类新的抗氧化药物，保护肾小球内皮细胞免受氧化应激的候选人。
Recently, increasing evidence suggests that the antihypertensive drug nifedipine acts as a protective agent for endothelial cells, and that the activity is unrelated to its calcium channel blocking. Nitrosonifedipine (NO-NIF) is metabolically and photo-chemically produced from nifedipine, and NO-NIF has been recognized as a contaminant of nifedipine because it has no antihypertensive effect. Treatment of tumor necrosis factor-a (TNF-alpha) suppressed the cell viability and facilitated the expression of Inter-Cellular Adhesion Molecule 1(ICAM-1) in human glomerular endothelial cells (HGECs) though, pretreatment of NO-NIF significantly recovered the TNF-alpha-induced cell damage to the same extent as Trolox-C did, and suppressed the ICAM-1 expression in a concentration dependent manner. In addition, NO-NIF inhibited the cell toxicity induced by cumene hydroperoxide, which hampers the integrity of cell membrane through oxidative stress, as effective as Trolox-c. These data suggest that NO-NIF is a candidate for a new class of antioxidative drug that protect cells against oxidative stress in glomerular endothelial cells.