Fernandes A C, Filipe P M, Manso C F
Instituto de Química Fisiológica, Faculdade de Medicina de Lisboa, Portugal.
Eur J Pharmacol. 1992 Sep 22;220(2-3):211-6. doi: 10.1016/0014-2999(92)90750-x.
The 21-aminosteroids, or lazaroids, are a novel class of antioxidant drugs designed to inhibit iron-dependent lipid peroxidation in biological lipid environments. They have been shown to be of therapeutic value in several animal models of traumatic, ischemic and hemorrhagic injury of the central nervous system. Our purpose was to evaluate the ability of 21-aminosteroids to protect human erythrocytes and plasma against oxidative damage in vitro. We found that the 21-aminosteroid U74500A inhibited erythrocyte and plasma lipid peroxidation. U74500A at 1 microM significantly reduced copper-induced and hydrogen peroxide-induced erythrocyte lipid peroxidation by 76.5 and 27.6%, respectively. The inhibition of erythrocyte lipid peroxidation was accompanied by an inhibition of hemolysis. Copper-induced plasma lipid peroxidation was also significantly reduced by as little as 1 microM U74500A. These results suggest that 21-aminosteroids may prove useful in preventive or therapeutic interventions in situations where erythrocyte or plasma components are subjected to oxidative stress and in situations related to copper-induced oxidative damage.
21-氨基类固醇,即拉扎罗ids,是一类新型抗氧化药物,旨在抑制生物脂质环境中依赖铁的脂质过氧化反应。在中枢神经系统创伤、缺血和出血性损伤的多种动物模型中,它们已显示出具有治疗价值。我们的目的是评估21-氨基类固醇在体外保护人红细胞和血浆免受氧化损伤的能力。我们发现21-氨基类固醇U74500A可抑制红细胞和血浆脂质过氧化。1微摩尔的U74500A分别使铜诱导和过氧化氢诱导的红细胞脂质过氧化显著降低76.5%和27.6%。红细胞脂质过氧化的抑制伴随着溶血的抑制。低至1微摩尔的U74500A也能显著降低铜诱导的血浆脂质过氧化。这些结果表明,在红细胞或血浆成分受到氧化应激的情况下以及与铜诱导的氧化损伤相关的情况下,21-氨基类固醇可能在预防或治疗干预中证明是有用的。