Misik V, Mak I T, Weglicki W B
Department of Medicine, George Washington University Medical Center, Washington, DC 20037.
Chem Biol Interact. 1992 Aug 14;83(2):97-105. doi: 10.1016/0009-2797(92)90039-n.
Nifedipine, which is unstable at light, is photolytically converted to the corresponding 4-[2'-nitrosophenyl]-pyridine (NTP). We reported earlier that NTP react with unsaturated lipids in a pseudo Diels-Alder reaction, thus forming stable nitroxide radicals. In this paper we report that superoxide is being generated in the latter reaction. Superoxide formation was evidenced by SOD-inhibitable cytochrome c reduction in the reaction of NTP with egg phosphatidylcholine at molar ratio 1:1, and 1:3. In this reaction an ESR-observable nitroxide radical was formed. Maximum nitroxide formation was observed after 90 min; the addition of SOD (93 units/ml) increased the concentration of nitroxide. This effect of SOD was reversed by catalase, indicating involvement of hydrogen peroxide in this effect. The nitroxide radical formation appears to be metal-independent, since neither iron salts, nor an iron chelator, desferal, influenced the nitroxide formation. Although production of superoxide in our system was only observed at high concentrations of NTP and of unsaturated lipids, this reaction may be of potential cytotoxic significance due to redox cycling of the nitroxide/hydroxylamine couple in cellular systems.
硝苯地平在光照下不稳定，会通过光解作用转化为相应的4-[2'-亚硝基苯基]-吡啶（NTP）。我们之前报道过，NTP会与不饱和脂质发生假狄尔斯-阿尔德反应，从而形成稳定的氮氧化物自由基。在本文中，我们报道了在后者的反应中会产生超氧阴离子。在NTP与蛋磷脂酰胆碱以1:1和1:3的摩尔比反应时，超氧阴离子的形成通过超氧化物歧化酶（SOD）可抑制的细胞色素c还原得以证明。在这个反应中形成了一种可用电子自旋共振（ESR）观测到的氮氧化物自由基。90分钟后观察到氮氧化物形成的最大值；添加SOD（93单位/毫升）会增加氮氧化物的浓度。过氧化氢酶可逆转SOD的这种作用，表明过氧化氢参与了这一作用。氮氧化物自由基的形成似乎与金属无关，因为铁盐和铁螯合剂去铁胺都不会影响氮氧化物的形成。尽管在我们的体系中仅在高浓度的NTP和不饱和脂质存在时才观察到超氧阴离子的产生，但由于细胞体系中氮氧化物/羟胺对的氧化还原循环，这个反应可能具有潜在的细胞毒性意义。
