Fukuhara Yayoi, Tsuchiya Koichiro, Horinouchi Yuya, Tajima Soichiro, Kihira Yoshitaka, Hamano Shuichi, Kawazoe Kazuyoshi, Ikeda Yasumasa, Ishizawa Keisuke, Tomita Shuhei, Tamaki Toshiaki
Department of Pharmacology, Institute of Health Bioscience, University of Tokushima Graduate School, Tokushima, Japan.
J Med Invest. 2011 Feb;58(1-2):118-26. doi: 10.2152/jmi.58.118.
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 photochemically 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-α (TNF-α) 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-α-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.
最近，越来越多的证据表明，抗高血压药物硝苯地平可作为内皮细胞的保护剂，且该活性与其钙通道阻滞作用无关。硝硝苯地平（NO-NIF）是由硝苯地平经代谢和光化学作用产生的，并且由于其没有抗高血压作用，NO-NIF已被认为是硝苯地平的一种污染物。肿瘤坏死因子-α（TNF-α）处理会抑制人肾小球内皮细胞（HGECs）的细胞活力，并促进细胞间黏附分子1（ICAM-1）的表达，然而，NO-NIF预处理可显著恢复TNF-α诱导的细胞损伤，程度与生育三烯酚-C相同，并以浓度依赖方式抑制ICAM-1的表达。此外，NO-NIF抑制了氢过氧化异丙苯诱导的细胞毒性，氢过氧化异丙苯通过氧化应激破坏细胞膜的完整性，其效果与生育三烯酚-c相同。这些数据表明，NO-NIF是一类新型抗氧化药物的候选者，可保护肾小球内皮细胞免受氧化应激。
