Therapeutic Effects of Liraglutide, Oxytocin and Granulocyte Colony-Stimulating Factor in Doxorubicin-Induced Cardiomyopathy Model: An Experimental Animal Study

• Published in: Cardiovascular toxicology 2019-12, Vol.19 (6), p.510-517
• Main Authors: Taskiran, Emin, Erdogan, Mümin Alper, Yigittürk, Gürkan, Erbas, Oytun
• Format: Article
• Language: English
• Subjects: Analysis; Anesthesia; Animals; Apoptosis; Apoptosis - drug effects; Biochemical analysis; Biomedical and Life Sciences; Biomedicine; C-Reactive Protein - metabolism; Calcium-binding protein; Cardiology; Cardiomyopathies - chemically induced; Cardiomyopathies - metabolism; Cardiomyopathies - pathology; Cardiomyopathies - prevention & control; Cardiomyopathy; Cardiotoxicity; Caspase; Caspase 3 - metabolism; Caspase-3; Colonies; Colony-stimulating factor; Disease Models, Animal; Doxorubicin; EKG; Electrocardiogram; Electrocardiography; Granulocyte colony-stimulating factor; Granulocyte Colony-Stimulating Factor - pharmacology; Granulocytes; Health aspects; Heart; Heart diseases; Heart Rate - drug effects; Humans; Inflammation; Inflammation Mediators - blood; Integrity; Leukocytes (granulocytic); Light microscopy; Lipid Peroxidation - drug effects; Liraglutide; Liraglutide - pharmacology; Malondialdehyde - blood; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Natriuretic Peptide, Brain - blood; Oncology; Oxidative Stress - drug effects; Oxytocin; Oxytocin - pharmacology; Pentraxins; Pharmacology/Toxicology; Rats, Sprague-Dawley; Rodents; Saline solutions; Serum Amyloid P-Component - metabolism; Signal Transduction; Sodium chloride; Tissues; Troponin; Troponin T; Troponin T - blood; Tumor Necrosis Factor-alpha - blood; Tumor necrosis factor-α; Type 2 diabetes
• ISSN: 1530-7905; 1559-0259
• DOI: 10.1007/s12012-019-09524-x

Doxorubicin-induced (DXR) cardiomyopathy is a serious health issue in oncology patients. Effective treatment of this clinical situation still remains to be discovered. In this experimental animal study, we aimed to define therapeutic effects of liraglutide, oxytocin and granulocyte colony-stimulating factor in DXR-induced cardiomyopathy model. 40 male Sprague–Dawley rats were included to study. 32 rats were given doxorubicin (DXR) for cardiomyopathy model. DXR was administered intraperitonally (i.p.) at every other day of 2.5 mg/kg/day at six times. Eight rats were taken as normal group and no treatment was performed. 32 rats given doxorubicin were divided into 4 groups. Group 1 rats were assigned to a placebo group and was given with a 0.9% NaCl saline solution at a dose of 1 ml/kg/day i.p. (DXR + saline), Group 2 rats were given with 1.8 mg/kg/day of Liraglutide i.p. (DXR + LIR), Group 3 rats were given with 160 μg/kg/day oxytocin i.p. (DXR + OX), Group 4 rats were given with 100 μg/kg/day filgrastim i.p. (DXR + G-CSF). All medications were given for 15 days. On day 16, under anesthesia, ECG was recorded from derivation I. After that, blood samples were taken by tail vein puncture for biochemical analysis. Finally, the animals were euthanized and the heart removed and prepared for immunohistochemical examination. All three treatments were shown to ameliorate the toxic effect of doxorubicin in cardiac tissue with the best results in DXR + OX group. DXR + OX group had the most preserved tissue integrity examined by light microscopy, least immune expression level of CASPASE-3 (5.3 ± 0.9) ( p