Comparative Cardiotoxicity of Low Doses of Digoxin, Ouabain, and Oleandrin
- PDF / 1,752,683 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 46 Downloads / 129 Views
Comparative Cardiotoxicity of Low Doses of Digoxin, Ouabain, and Oleandrin Ana F. M. Botelho1 · Ana L. S. Miranda2 · Thalita G. Freitas2 · Paula F. Milani2 · Tatiane Barreto3 · Jáder S. Cruz3 · Marília M. Melo2
© Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The aim of this study was to evaluate the comparative effects of CGs on heart physiology. Twenty-eight Wistar rats were distributed into four groups (n = 7), control group received NaCl 0.9% every 24 h for 21 days; treated groups received respectively 50 μg/kg of digoxin (DIG), ouabain (OUA) and oleandrin (OLE) every 24 h for 21 days. Serial ECGs were performed, as well as serum levels of creatinine kinase (CK), its MB fraction, troponin I (cTnI), calcium ( Ca2+) and lactic dehydrogenase (LDH). Heart tissue was processed for histology, scanning electron microscopy and Western blot analysis for cTnI, brain natriuretic peptide (BNP), sodium potassium pump alpha-1 and alpha-2. Ventricle samples were also analyzed for thiobarbituric acid reactive substances and antioxidant enzymes (SOD, GPX, and CAT). ECGs showed decrease in QT and progressive shortening of QRS. No arrhythmias were observed. No significant differences were associated with CGs treatment and serum levels of CK, CK-MB, and cTnI. Only oleandrin increased LDH levels. Histological analysis showed degenerative changes and only oleandrin promoted moderate focal necrosis of cardiomyocytes. Scanning microscopy also confirmed the greatest effect of oleandrin, with rupture and shortening of cardiac fibers. The expression of troponin I and alpha-1 isoform were not altered, however, the protein levels of BNP and alpha-2 were higher in the groups that received oleandrin and ouabain in relation to the digoxin group. All GCs affected the production of ROS, without causing lipid peroxidation, through the activation of different antioxidant pathways. It is concluded that the administration of digoxin, ouabain, and oleandrin at 50 µg/kg for 21 days caused cardiovascular damage that represent an important limitation into its future use in heart failure and antineoplastic therapy. Keywords Cardenolides · Cardiac glycosides · Oxidative stress · Rat
Introduction
Handling Editor: Gen Suzuki . * Ana F. M. Botelho [email protected] 1
Department of Veterinary Medicine, College of Veterinary and Zootecnia, Universidade Federal de Goiás, Goiânia, Goiás, Brazil
2
Department of Veterinary Clinic and Surgery, College of Veterinary, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
3
Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
Cardiac glycosides (CGs) are well-known substances frequently used in the treatment of heart failure (HF) [1, 3]. The proposed mechanism of action of CGs is the inhibition of the sodium and potassium ATPase (NKA) current, leading to an increase in intracellular sodium (Na+). The immediate consequence of such rise is the escalation of cardiomyocyte i
Data Loading...
