Ruggiero A C, Nepomuceno M F, Jacob R F, Dorta D J, Tabak M
Faculdade de Engenharias e Ciências Químicas, UNIMEP, 13400-901, Piracicaba, SP, Brazil.
Physiol Chem Phys Med NMR. 2000;32(1):35-48.
The antioxidant effects of dipyridamol (DIP), a coronary vasodilator, and its derivative RA-25 were compared in intact red blood cells (RBC) and in isolated ghost membranes. Both compounds are quite effective antioxidants in cumene hydroperoxide-induced lipid peroxidation of RBC, showing a much smaller effect for hydrogen peroxide oxidation. The antioxidant effect of DIP was considerably higher than that of RA25. For isolated ghost membranes, the apparent IC50 (the drug concentration that produces 50% inhibition of lipid peroxidation) in cumene hydroperoxide-induced peroxidation was 25 microM, while the maximum protective effect of RA-25 was around 30% in the drug concentration range of 50-100 microM. The drugs can protect the oxidative hemolysis induced by cumene hydroperoxide with a lower effect when the hemolysis is induced by H2O2. The significant antioxidant effect against damages induced by cumene hydroperoxide suggests that DIP, due to its lipophilic character, can interact with RBC membranes, and the protective effect is associated with the binding of the drug to the membrane. On the other hand, RA-25 is more hydrophilic than DIP, binds to the membrane to a smaller extent, and, for this reason, has a lower antioxidant effect.
比较了冠状动脉扩张剂双嘧达莫（DIP）及其衍生物RA - 25在完整红细胞（RBC）和分离的血影膜中的抗氧化作用。两种化合物在异丙苯过氧化氢诱导的红细胞脂质过氧化中都是相当有效的抗氧化剂，而过氧化氢氧化时效果要小得多。DIP的抗氧化作用明显高于RA25。对于分离的血影膜，异丙苯过氧化氢诱导的过氧化反应中，表观IC50（产生50%脂质过氧化抑制的药物浓度）为25微摩尔，而在50 - 100微摩尔的药物浓度范围内，RA - 25的最大保护作用约为30%。这些药物可以保护由异丙苯过氧化氢诱导的氧化溶血，而由过氧化氢诱导溶血时效果较低。对异丙苯过氧化氢诱导的损伤具有显著的抗氧化作用表明，由于DIP的亲脂性，它可以与红细胞膜相互作用，其保护作用与药物与膜的结合有关。另一方面，RA - 25比DIP亲水性更强，与膜的结合程度较小，因此抗氧化作用较低。
