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.