Cardiometabolic efficacy and toxicological evaluation of a pharmacological galanin receptor agonist

Serebryakova L.I.1, Studneva I.M.1, Ovchinnikov M.V.1, Veselova O.M.1, Molokoedov A.S.1, Arzamastsev E.V.1, Afanasyeva E.Yu.1, Terekhova O.A.1, Sidorova M.V.1, Pisarenko O.I.1

1. National Medical Research Center for Cardiology, Moscow, Russia
Section: Experimental Study
DOI: 10.18097/PBMC20196503231      PubMed Id: 31258147
Year: 2019  Volume: 65  Issue: 3  Pages: 231-238
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.
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Keywords: modified galanin fragment, rat, myocardial ischemia and reperfusion, myocardial energy metabolism, toxicity

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.
This paper is also available as the English translation: 10.1134/S1990750819040097
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