The use of the anticancer
drug doxorubicin (Dox) is limited due to its cardiotoxic effect. Using the method of automatic solid-phase peptide synthesis, we obtained a synthetic agonist of
galanin receptors GalR1-3 [RAla14, His15]-galanine (2-15) (G), exhibiting cardioprotective properties. It was purified by high performance liquid chromatography (HPLC). The homogeneity and structure of the
peptide was confirmed by HPLC, 1H-NMR spectroscopy and mass spectroscopy. The purpose of this study was to study the effect of G on the metabolism and cardiac function of rats with chronic
heart failure (CHF) caused by Dox. Experiments were performed using male Wistar rats weighing 280-300 g. The control group of animals (C) was intraperitoneally treated with saline for 8 weeks; the
doxorubicin group (D) of rats was intraperitoneally treated with Doх; the group of Doх +
peptide G (D+G) received intraperitoneally
injections of Doх and subcutaneously
injections of
peptide G; the
peptide G group (G) was subcutaneously treated with G. At the beginning and at the end of the study, the concentration of
thiobarbituric acid reactive substances (
TBARS) and the activity of
creatine kinase-MB (CK-MB) were determined in blood plasma; the animals were weighed, and cardiac function was assessed using echocardiography. At the end of the experiments, the hearts were used for determination of metabolites and assessment of oxidative phosphorylation in mitochondria. After 8-week treatment, animals of group D were characterized by severe
heart failure, the lack of
weight gain and an increase in plasma
TBARS concentration and CK-MB activity. These disorders were accompanied by a decrease in the content of myocardial high-energy
phosphates, a reduction inmitochondrial respiratory parameters, accumulation of
lactate and
glucose in the heart, and disturbances in the metabolism of
alanine and glutamic and aspartic
acids. Coadministration of G and Dox prevented the increase in plasma CK-MB activity and significantly reduced the plasma
TBARS concentration. At the end of the experiments animals of group D+G had higher myocardial energy state and the respiratory control index of mitochondria than animals of group D, there was a decrease in anaerobic glycolysis and no changes in the
amino acid content compared to the control. The
peptide G significantly improved the parameters of cardiac function and caused
weight gain in animals of group D+G in comparison with these parameters in group D. The obtained results demonstrate the ability of a novel agonist of
galanin receptors GalR1-3 to attenuate Dox-indiced
cardiotoxicity.