Chimeric Agonist of Galanin Receptor GALR2 Reduces Heart Damage in Rats with Streptozotocin-Induced Diabetes

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Irina M. Studneva¹, Oksana M. Veselova¹, Igor V. Dobrokhotov¹, Larisa I. Serebryakova¹, Marina E. Palkeeva¹, Alexander S. Molokoedov¹, Andrey A. Azmuko¹, Michael V. Ovchinnikov¹, Maria V. Sidorova¹, and Oleg I. Pisarenko^1,a*

¹National Medical Research Center for Cardiology, 121552 Moscow, Russia

^* To whom correspondence should be addressed.

Received May 15, 2021; Revised February 28, 2022; Accepted February 28, 2022

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Neuropeptide galanin and its N-terminal fragments reduce the generation of reactive oxygen species and normalize metabolic and antioxidant states of myocardium in experimental cardiomyopathy and ischemia/reperfusion injury. The aim of this study was to elucidate the effect of WTLNSAGYLLGPβAH-OH (peptide G), a pharmacological agonist of the galanin receptor GalR2, on the cardiac injury induced by administration of streptozotocin (STZ) in rats. Peptide G was prepared by solid phase peptide synthesis using the Fmoc strategy and purified by preparative HPLC; its structure was confirmed by ¹H-NMR spectroscopy and MALDI-TOF mass spectrometry. Experimental animals were randomly distributed into five groups: C, control; S, STZ-treated; SG10, STZ + peptide G (10 nmol/kg/day); SG50, STZ + peptide G (50 nmol/kg/day); G, peptide G (50 nmol/kg/day). Administration of peptide G prevented hyperglycemia in SG50 rats. By the end of the experiment, the ATP content, total pool of adenine nucleotides, phosphocreatine (PCr) content, and PCr/ATP ratio in the myocardium of animals of the SG50 group were significantly higher than in rats of the S group. In the SG50 and SG10 groups, the content of lactate and lactate/pyruvate ratio in the myocardium were reduced, while the glucose content was increased vs. the S group. Both doses of peptide G reduced the activation of creatine kinase-MB and lactate dehydrogenase, as well as the concentration of thiobarbituric acid reactive products in the blood plasma of STZ-treated rats to the control values. Taken together, these results suggest that peptide G has cardioprotective properties in type 1 diabetes mellitus. Possible mechanisms of peptide G action in the STZ-induced diabetes are discussed.

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KEY WORDS: galanin, heart, streptozotocin, myocardial metabolism, lipid peroxidation, cardiomyocyte membranes

DOI: 10.1134/S0006297922040046

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