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The Mechanisms of Cardiac Protection Using a Synthetic Agonist of Galanin Receptors during Chronic Administration of Doxorubicin
- Source :
- Acta Naturae
- Publication Year :
- 2020
- Publisher :
- A.I. Gordeyev, 2020.
-
Abstract
- The use of the anticancer drug doxorubicin (Dox) is limited by its cardiotoxic effect. The aim of this work was to study the effect of a new synthetic agonist of the galanin receptor GalR1-3 [Ala14, His15]-galanine (215) (G) on the metabolism, antioxidant enzyme activity, and cardiac function in rats with cardiomyopathy (CM) caused by chronic administration of Dox. Coadministration of peptide G and Dox significantly increased the fractional shortening (FS) and ejection fraction (EF) by an average of 30 4% compared with the indices in the Dox group. The reduced severity of cardiac dysfunction under the action of G was accompanied by a 2.5-fold decrease in the activity of creatine kinase-MB (CK-MB) in blood plasma. The protective mechanism of the action of peptide G is caused by a reduced lipid peroxidation (LP) that is due to the increased activity of Cu,Zn superoxide dismutase (Cu,Zn-SOD) and glutathione peroxidase (GSH-Px) in the damaged heart. Administration of peptide G significantly increased the adenine nucleotide pool (AH), ATP content, and the levels of phosphocreatine (PCr) and total creatine (Cr) in the damaged myocardium. It also reduced lactate accumulation relative to its content in the Dox group. The better energy supply of cardiomyocytes after treatment with peptide G prevented the accumulation of cytotoxic ammonia and disruption in the metabolism of the key myocardial amino acids (glutamic acid (Glu), aspartic acid (Asp), and alanine (Ala)). Peptide G significantly improved the morphological parameters of the heart in rats treated with Dox. The results show promise in using peptide G to efficiently correct functional, morphological, and metabolic damage to the heart caused by anthracycline chemotherapy.
- Subjects :
- 0301 basic medicine
Agonist
medicine.drug_class
Galanin receptor
Pharmacology
Creatine
Biochemistry
doxorubicin
Phosphocreatine
Lipid peroxidation
myocardial metabolism
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Adenine nucleotide
antioxidant enzymes
medicine
rat
Galanin
Molecular Biology
chemistry.chemical_classification
galanin
Chemistry
Glutathione peroxidase
030104 developmental biology
030220 oncology & carcinogenesis
Molecular Medicine
Biotechnology
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 20758251
- Volume :
- 12
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Acta Naturae
- Accession number :
- edsair.doi.dedup.....1707350dafb0fd84e47f992128cb4090