The anti-ischemic and antioxidant activity of the pharmacological agonist of galanin receptor GalR2 and carnosine in in vitro and in vivo model systems

Serebryakova L.I.1, Studneva I.M.1, Veselova O.M.1, Dobrokhotov I.V.1, Konovalova G.G.1, Timoshin A.A.1, Abramov A.A.1, Avdeev D.V.1, Sidorova M.V.1, Lankin V.Z.1, Pisarenko O.I.1

1. National Medical Research Center for Cardiology, Moscow, Russia
Section: Experimental Study
DOI: 10.18097/PBMC20226803190      PubMed Id: 35717583
Year: 2022  Volume: 68  Issue: 3  Pages: 190-200
Antioxidant and anti-ischemic properties of the pharmacological agonist of galanin receptor GalR2 WTLNSAGYLLGPβAH (Gal) and its C-terminal fragment, dipeptide carnosine (βAH), were studied in the model of regional ischemia and reperfusion of the rat heart in vivo in the dose range of 0.5-5.0 mg/kg and Cu²⁺-induced free radical oxidation of low density lipoproteins (LDL) of human plasma in vitro for peptide concentrations of 0.01 mM and 0.1 mM. Gal was obtained by automatic solid phase synthesis using the Fmoc methodology; its structure was characterized by 1H-NMR spectroscopy and MALDI-TOF mass spectrometry. Intravenous administration of the optimal dose of Gal (1 mg/kg) to rats after ischemia was more effective than carnosine in reducing of the myocardial infarct size and the activity of creatine kinase-MB and lactate dehydrogenase in blood plasma at the end of reperfusion. It also improved the metabolic state of the reperfused myocardium and reduced the formation of peroxidation products during reperfusion. Gal reduced more effectively the formation of adducts of hydroxyl radicals in the interstitium of the area at risk (AAR) of the rat heart than carnosine. Carnosine at a dose of 1 mg/kg more effectively increased the activity of catalase and glutathione peroxidase in the AAR by the end of reperfusion compared to Gal. In a model of Cu²⁺-initiated oxidation of human plasma LDL 0.1 mM carnosine demonstrated a significantly more pronounced reduction in the formation of lipid radicals compared to Gal. The results show that Gal can be considered as a promising agent that reduces myocardial injury during reperfusion and oxidative stress.
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Keywords: galanin, carnosine, rat, cardiac ischemia and reperfusion, myocardial infarction, cardiac energy state, lipid peroxidation, antioxidant enzymes

Serebryakova, L. I., Studneva, I. M., Veselova, O. M., Dobrokhotov, I. V., Konovalova, G. G., Timoshin, A. A., Abramov, A. A., Avdeev, D. V., Sidorova, M. V., Lankin, V. Z., Pisarenko, O. I. (2022). The anti-ischemic and antioxidant activity of the pharmacological agonist of galanin receptor GalR2 and carnosine in in vitro and in vivo model systems. Biomeditsinskaya Khimiya, 68(3), 190-200.
This paper is also available as the English translation: 10.1134/S1990750822040072
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