The goal of this study was to examine effects of a novel galanin receptor agonist GalR1-3 [bAla14, His15]-galanine 2-15 (G), obtained by automatic solid-phase synthesis, on the metabolic state of the area at risk and the size of acute myocardial infarction (MI) in rats in vivo and evaluate its toxicity in BALB /c mice. In anesthetized rats, regional ischemia was simulated by coronary artery occlusion and then coronary blood flow was restored. The peptide G was administered intravenously (i.v.) with a bolus after a period of regional ischemia in the dose range of 0.25-3.0 mg/kg. The sizes of MI and the activities of creatine kinase-MB (СK-MB) and lactate dehydrogenase (LDH) in blood plasma were estimated. The effect of administration of the optimal dose of G (1.0 mg/kg) on myocardial content of adenine nucleotides (AN), phosphocreatine (PCr), creatine (Cr) and lactate was studied. I.v. administration of G to rats at a dose of 1.0 mg/kg slightly affected hemodynamic parameters, but reduced MI size by 40% and decreased plasma LDH and CK-MB activity by the end of reperfusion compared to control. These effects were accompanied by a significant improvement in energy state of area at risk (AAR) – an increase in myocardial content of ATP, åAN, PCr and åCr, and combined with a decrease in myocardial lactate level compared with the control. Toxicity of peptide G was studied with a single intraperitoneal injection of 0.5-3.0% solution of the peptide substance to mice. The absence of signs of intoxication and death of animals after G injection in the maximum possible dose did not allow determining the value of the average lethal dose. The results indicate therapeutic potential of the peptide G for preventing myocardial ischemia and reperfusion injury and feasibility for further study of its pharmacological properties and mechanisms of action.
Keywords: modified galanin fragment, rat, myocardial ischemia and reperfusion, myocardial energy metabolism, toxicity
Serebryakova L.I. et al. Cardiometabolic efficacy and toxicological evaluation of a pharmacological galanin receptor agonist // Biomeditsinskaya khimiya. - 2019. - V. 65. -N 3. - P. 231-238.
Serebryakova L.I. et al., "Cardiometabolic efficacy and toxicological evaluation of a pharmacological galanin receptor agonist." Biomeditsinskaya khimiya 65.3 (2019): 231-238.
Serebryakova, L. I., Studneva, I. M., Ovchinnikov, M. V., Veselova, O. M., Molokoedov, A. S., Arzamastsev, E. V., Afanasyeva, E. Yu., Terekhova, O. A., Sidorova, M. V., Pisarenko, O. I. (2019). Cardiometabolic efficacy and toxicological evaluation of a pharmacological galanin receptor agonist. Biomeditsinskaya khimiya, 65(3), 231-238.
Timotin A., Pisarenko O., Sidorova M., Studneva I., Shulzhenko V., Palkeeva M., Serebryakova L., Molokoedov A., Veselova O., Cinato M., Tronchere H., Boal F., Kunduzova O. (2017) Oncotarget, 8(13), 21241-21252. CrossRef Scholar google search