De La Cruz J P, Villalobos M A, Carrasco T, Smith-Agreda J M, Sánchez de la Cuesta F
Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Spain.
Brain Res. 1992 Dec 4;597(2):250-6. doi: 10.1016/0006-8993(92)91481-s.
The effects of pyrimido-pyrimidine derivatives (dipyridamole, RA-642 and mopydamole) on lipid peroxidation (inhibition of the production of malondialdehyde, MDA) in different regions of the rat brain were studied. Ferrous sulfate and ascorbic acid (FeAs) were used to induce lipid peroxidation via the formation of hydroxyl anions. The antiperoxidative effect of RA-642 (in the microM range) was 10 times more potent than that of dipyridamole. Mopydamole did not exert any inhibitory effect on MDA production. In a model of ischemia reperfusion with bilateral occlusion of the common carotid arteries for 1 h and restoration of circulation for a period of 2 h, dipyridamole inhibited FeAs-induced MDA production but did not protect from postischemic brain tissue damage (measured by mitochondrial reduction of tetraphenyl tetrazolium). RA-642 inhibited FeAs-induced MDA production and showed 50-67% protection from tissue damage as compared with untreated animals, while mopydamole did not inhibit MDA production and showed 30-48% protection. No correlation was found between inhibition of lipid peroxidation and protection from brain tissue damage.
研究了嘧啶并嘧啶衍生物（双嘧达莫、RA - 642和莫匹达莫）对大鼠脑不同区域脂质过氧化作用（抑制丙二醛，MDA的产生）的影响。硫酸亚铁和抗坏血酸（FeAs）用于通过形成羟基阴离子诱导脂质过氧化。RA - 642（在微摩尔范围内）的抗过氧化作用比双嘧达莫强10倍。莫匹达莫对MDA的产生没有任何抑制作用。在双侧颈总动脉闭塞1小时并恢复循环2小时的缺血再灌注模型中，双嘧达莫抑制FeAs诱导的MDA产生，但不能保护免受缺血后脑组织损伤（通过四苯基四氮唑的线粒体还原测定）。与未处理的动物相比，RA - 642抑制FeAs诱导的MDA产生，并显示出50 - 67%的组织损伤保护作用，而莫匹达莫没有抑制MDA产生，显示出30 - 48%的保护作用。在脂质过氧化抑制与脑组织损伤保护之间未发现相关性。
