Mak I T, Boehme P, Weglicki W B
Department of Medicine, George Washington University Medical Center, Washington, D.C.
Circ Res. 1992 Jun;70(6):1099-103. doi: 10.1161/01.res.70.6.1099.
The effects of four calcium channel blockers (nicardipine, nifedipine, verapamil, and diltiazem) on free radical injury in cultured endothelial cells were studied and compared with those of butylated hydroxytoluene. When the cultured cells were exposed to a superoxide and hydroxyl radical generating system for up to 60 minutes, lipid peroxidation occurred, and cellular viability decreased by 60% at 30 minutes. Concomitantly, total cellular glutathione decreased by 40%, whereas total protein thiols changed minimally. Preincubation of the cells with each of the calcium blockers (5 and 20 microM) before free radical addition resulted in various degrees of significant protection against cell death, and losses of glutathione correlated significantly (r = 0.89, p less than 0.001). The order of efficacy was nicardipine greater than nifedipine greater than verapamil greater than diltiazem; butylated hydroxytoluene was about fourfold more potent than nicardipine. Because none of the agents affected the level of hydroxyl radicals generated in the aqueous phase, the data suggest that the protective mechanisms were mediated by their lipid antiperoxidative activities, which also prevented the glutathione decrease caused by inhibition of peroxide generation.
研究了四种钙通道阻滞剂（尼卡地平、硝苯地平、维拉帕米和地尔硫䓬）对培养的内皮细胞自由基损伤的影响，并与丁基羟基甲苯的作用进行了比较。当将培养的细胞暴露于超氧化物和羟基自由基生成系统长达60分钟时，发生了脂质过氧化，细胞活力在30分钟时下降了60%。与此同时，细胞内总谷胱甘肽减少了40%，而总蛋白巯基变化极小。在添加自由基之前，用每种钙阻滞剂（5和20微摩尔）对细胞进行预孵育，可对细胞死亡产生不同程度的显著保护作用，且谷胱甘肽的损失具有显著相关性（r = 0.89，p < 0.001）。疗效顺序为尼卡地平>硝苯地平>维拉帕米>地尔硫䓬；丁基羟基甲苯的效力约为尼卡地平的四倍。由于这些药物均未影响水相中产生的羟基自由基水平，数据表明其保护机制是由其脂质抗过氧化活性介导的，这也防止了因过氧化物生成受抑制而导致的谷胱甘肽减少。
