Antioxidant Properties of Galanin and Its N-Terminal Fragments in in vitro and in vivo Oxidative Stress Modeling

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Oleg I. Pisarenko^1,a*, Irina M. Studneva¹, Larisa I. Serebryakova¹, Alexandr A. Timoshin¹, Galina G. Konovalova¹, Vadim Z. Lankin¹, Alla K. Tihaze¹, Oksana M. Veselova¹, Igor V. Dobrokhotov¹, Roman O. Lyubimov¹, Mariya V. Sidorova¹, Marina E. Palkeeva¹, and Alexandr S. Molokoedov¹

¹National Medical Research Center for Cardiology, Ministry of Health of the Russian Federation, 121552 Moscow, Russia

^* To whom correspondence should be addressed.

Received December 21, 2020; Revised February 4, 2021; Accepted February 8, 2021

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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.

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KEY WORDS: galanin, heart, ischemia and reperfusion, necrosis, lipid peroxidation, antioxidant enzymes, cardiomyocyte membrane damage

DOI: 10.1134/S0006297921040106

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