Lukk M V, Zarubina I V, Shabanov P D
Eksp Klin Farmakol. 2009 Jul-Aug;72(4):36-42.
The antihypoxic activity of six aminothiol and triazinoindole derivatives was studied on a model of hypobaric (hypoxic) hypoxia in rats. With respect to the antihypoxic activity, the compounds can be arranged in the following order: amtizole succinate = amtizole approximately equal to gutimine > T-475 > gutimine > succinate succinate. One of the possible mechanisms of action for all antyhypoxants is the inhibition of lipid peroxidation and recovery of hypoxia-induced antioxidant defense system in the brain, kidneys, liver, myocardium, and muscles, which results in reduction of the contents of malonic dialdehyde and lipid hydroperoxides and an increase in the activity of superoxide dismutase and the content of recovered glutathione. Amtizole showed the most pronounced antihypoxic activity and eliminated all negative shifts caused by moderate and heavy hypoxia in the organs studied. Succinic acid did not potentiate the antihypoxic and antioxidant properties of amtizole. Gutimine inhibited the activation of lipid peroxidation and prevented the accumulation of malonic dialdehyde and lipid hydroperoxides and the decrease of recovered glutathione caused by hypoxia in all organs studied. In addition, gutimine inhibited the activity of both superoxide dismutase and catalase. Gutimine succinate exhibited enhanced inhibitory action (as compared to that of gutimine) on lipid peroxidation and removed the inhibition of superoxide dismutase activity in all organs studied. Thus, the present study revealed a parallelism in the antihypoxic and antioxidant effects of aminothiol and triazinoindole derivatives.
在大鼠低压（低氧）低氧模型上研究了六种氨基硫醇和三嗪并吲哚衍生物的抗缺氧活性。就抗缺氧活性而言，这些化合物可按以下顺序排列：琥珀酸氨替唑 = 氨替唑 ≈ 古替明 > T - 475 > 古替明 > 琥珀酸酯。所有抗缺氧剂可能的作用机制之一是抑制脂质过氧化并恢复大脑、肾脏、肝脏、心肌和肌肉中缺氧诱导的抗氧化防御系统，这导致丙二醛和脂质氢过氧化物含量降低，超氧化物歧化酶活性增加以及还原型谷胱甘肽含量增加。氨替唑表现出最显著的抗缺氧活性，并消除了中度和重度缺氧对所研究器官造成的所有负面变化。琥珀酸并未增强氨替唑的抗缺氧和抗氧化特性。古替明抑制脂质过氧化的激活，并防止所研究的所有器官中因缺氧导致的丙二醛和脂质氢过氧化物的积累以及还原型谷胱甘肽的减少。此外，古替明抑制超氧化物歧化酶和过氧化氢酶的活性。琥珀酸古替明对脂质过氧化表现出增强的抑制作用（与古替明相比），并消除了所研究的所有器官中超氧化物歧化酶活性的抑制。因此，本研究揭示了氨基硫醇和三嗪并吲哚衍生物的抗缺氧和抗氧化作用的平行性。
