Alam M S, Ku K, Yamauchi M, Hashimoto M, Nosaka S, Hossain M S, Masumura S, Nakayama K, Tamura K
First Department of Surgery, Shimane Medical University, Izumo, Japan.
Mol Cell Biochem. 1998 Jan;178(1-2):237-43. doi: 10.1023/a:1006855917392.
Recently, we have reported that a new synthetic compound, 1,2bis(nicotinamido)-propane (nicaraven), improved cardiac function following preservation and reperfusion. In this study, we investigated the efficacy of nicaraven as a radical scavenger by using an in vitro model of oxidative stress, to clarify mechanisms of the protective effect of this new compound on reperfusion injury in rat heart. Ring segments of epicardial right coronary arteries (RCA) of pig were suspended in organ chambers and exposed to hydroxyl radicals (.OH), generated (by two different systems) by 0.28 mM FeSO4/0.28 mM H2O2 and DHF/Fe3+-ADP (2.4 mM, 43 nM, and 1.56 uM, respectively) to the bathing solution for 60 min. Prior exposure of the coronary arteries to .OH significantly produced right-ward shift of the dose-response curves of the bradykinin-induced endothelium-dependent relaxations (an increase in the ED50 value for bradykinin by 4.37 and 1.98 times than control in two different .OH generating systems, respectively), but did not affect the maximum relaxation responses. The presence of nicaraven (10(-4) and 10(-5) M) in the .OH generating system, shifted the dose-response curves to bradykinin to the control level, suggesting a significant hydroxyl radical scavenging effect of the drug. These results indicate that nicaraven, a new hydroxyl radical scavenger, exhibits a protective effect on hydroxyl radical-induced endothelial dysfunctions of pig coronary artery.
最近，我们报道了一种新的合成化合物1,2-双（烟酰胺基）丙烷（尼卡瑞文）在心脏保存和再灌注后可改善心脏功能。在本研究中，我们通过使用氧化应激的体外模型研究了尼卡瑞文作为自由基清除剂的功效，以阐明这种新化合物对大鼠心脏再灌注损伤保护作用的机制。将猪的心外膜右冠状动脉（RCA）环段悬挂在器官浴槽中，并暴露于由0.28 mM硫酸亚铁/0.28 mM过氧化氢和二氢黄酮/铁离子-二磷酸腺苷（分别为2.4 mM、43 nM和1.56 μM）通过两种不同系统产生的羟自由基（·OH）中60分钟。冠状动脉预先暴露于·OH会显著使缓激肽诱导的内皮依赖性舒张的剂量反应曲线向右移动（在两种不同的·OH产生系统中，缓激肽的半数有效剂量值分别比对照增加4.37倍和1.98倍），但不影响最大舒张反应。在·OH产生系统中加入尼卡瑞文（10⁻⁴和10⁻⁵ M）可使缓激肽的剂量反应曲线恢复到对照水平，表明该药物具有显著的羟自由基清除作用。这些结果表明，新型羟自由基清除剂尼卡瑞文对羟自由基诱导的猪冠状动脉内皮功能障碍具有保护作用。
