Abstract

Antioxidant properties of rat galanin GWTLNSAGYLLGPHAIDNHRSFSDKHGLT-NH₂ (Gal), N-terminal fragment of galanin (2-15 aa) WTLNSAGYLLGPHA (G1), and its modified analogue WTLNSAGYLLGPβAH (G2) were studied in vivo in the rat model of regional myocardial ischemia and reperfusion and in vitro in the process of Cu²⁺-induced free radical oxidation of human blood plasma low-density lipoproteins. Intravenous administration of G1, G2, and Gal to rats after ischemia induction reduced the infarction size and activities of the necrosis markers, creatine kinase-MB and lactate dehydrogenase, in blood plasma at the end of reperfusion. G1, G2, and Gal reduced formation of the spin adducts of hydroxyl radicals in the interstitium of the area at risk during reperfusion, moreover, G2 and Gal also reduced formation of the secondary products of lipid peroxidation in the reperfused myocardium. It was shown in the in vivo experiments and in the in vitro model system that the ability of galanin peptides to reduce formation of ROS and attenuate lipid peroxidation during myocardial reperfusion injury was not associated directly with their effects on activities of the antioxidant enzymes of the heart: Cu,Zn-superoxide dismutase, catalase, and glutathione peroxidase. The peptides G1, G2, and Gal at concentrations of 0.01 and 0.1 mM inhibited Cu²⁺-induced free radical oxidation of human low-density lipoproteins in vitro. The results of oxidative stress modeling demonstrated that the natural and synthetic agonists of galanin receptors reduced formation of the short-lived ROS in the reperfused myocardium, as well as of lipid radicals in blood plasma. Thus, galanin receptors could be a promising therapeutic target for cardiovascular diseases.

中文翻译：

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甘丙肽及其N末端片段在体外和体内氧化应激模型中的抗氧化性能

摘要

在区域性心肌缺血的大鼠模型中体内研究了大鼠甘丙肽GWTLNSAGYLLGPHAIDNHRSFSDKHGLT-NH ₂（Gal），甘丙肽N末端片段（2-15 aa）WTLNSAGYLLGPHA（G1）及其修饰的类似物WTLNSAGYLLGPβAH（G2）的抗氧化特性。和再灌注以及体外Cu ²⁺的过程诱导的人血浆低密度脂蛋白的自由基氧化。缺血诱导后对大鼠静脉内施用G1，G2和Gal可以减少再灌注结束时血浆中的梗塞面积和坏死标记肌酸激酶MB和乳酸脱氢酶的活性。G1，G2和Gal减少了在再灌注期间处于危险中的区域的间质中羟自由基的自旋加合物的形成，此外，G2和Gal还减少了再灌注心肌中脂质过氧化的副产物的形成。它已在体内实验和体外显示甘丙肽减少心肌再灌注损伤过程中ROS的形成和减弱脂质过氧化作用的能力的模型系统，与它们对心脏抗氧化酶的活性没有直接关系：铜，锌超氧化物歧化酶，过氧化氢酶和谷胱甘肽过氧化物酶。肽G1，G2，和Gal在0.01和0.1mM的浓度抑制铜²⁺诱导的人的低密度脂蛋白的氧化自由基体外。氧化应激建模的结果表明，甘丙肽受体的天然和合成激动剂减少了再灌注心肌中短寿命ROS的形成以及血浆中脂质自由基的形成。因此，甘丙肽受体可能是心血管疾病的有希望的治疗靶标。