Antioxidant Effects of Photodegradation Product of Nifedipine
Antioxidant Effects of Photodegradation Product of Nifedipine
复制标题
DOI：
10.1248/cpb.59.208
复制
发表时间：
2011-02-01
影响因子：
1.7
通讯作者：
Tamaki, Toshiaki
中科院分区：
文献类型：
--
作者：
Horinouchi, Yuya;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内皮细胞的保护剂，其活性与其钙通道阻断无关。硝苯地平在光照下不稳定，据报道可分解为稳定的亚硝基硝苯地平（NO-NIF）。no - nw无降压作用，已被认定为硝苯地平的污染物。本研究首次证明，当NO-NIF与人脐静脉内皮细胞（HUVECs）相互作用时，它以一种时间依赖性的方式转变为NO-NIF自由基。在HUVECs中，NO-NIF自由基的电子顺磁共振（EPR）信号呈不对称模式，表明自由基位于膜内。NO-NIF自由基对1,1-二苯基-2-吡啶肼基有清除活性，而NO-NIF和硝苯地平均无清除活性。此外，NO-NIF自由基比NO-NIF或硝苯地平更有效地淬灭脂质过氧化物。此外，NO-NIF还能减弱LY83583刺激的HUVECs中超氧化物自由基，抑制铁-硝基三乙酸（Fe-NTA）诱导的大鼠嗜铬细胞瘤（PC12）细胞毒性。我们的研究结果表明，NO-NIF是一类新的抗氧化药物的候选者，可以保护细胞免受氧化应激的影响。
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. Nifedipine is unstable under light and reportedly decomposes to a stable nitrosonifedipine (NO-NIF). NO-NW has no antihypertensive effect, and it has been recognized as a contaminant of nifedipine. The present study for the first time demonstrated that NO-NIF changed to a NO-NIF radical in a time-dependent manner when it interacted with human umbilical vein endothelial cells (HUVECs). The electron paramagnetic resonance (EPR) signal of NO-NIF radicals in HUVECs showed an asymmetric pattern suggesting that the radicals were located in the membrane. The NO-NIF radicals had radical scavenging activity for 1,1-diphenyl-2-picrylhydrazyl, whereas neither NO-NIF nor nifedipine did. In addition, the NO-NIF radical more effectively quenched lipid peroxides than NO-NIF or nifedipine. Furthermore, NO-NIF attenuated the superoxide-derived free radicals in HUVECs stimulated with LY83583, and suppressed iron-nitrilotriacetic acid (Fe-NTA)-induced cytotoxicity in rat pheochromocytoma (PC12) cells. Our findings suggest that NO-NIF is a candidate for a new class of antioxidative drugs that protect cells against oxidative stress.