Redox-Active Drug, MnTE-2-PyP5+, Prevents and Treats Cardiac Arrhythmias Preserving Heart Contractile Function
Joint Authors
Gomes, Enéas R. M.
de Araújo, Juliana Sousa Soares
Mattos, Sandra da Silva
Araújo, Demetrius A. M.
Menezes-Filho, José Evaldo Rodrigues de
Souza, Diego Santos de
Vasconcelos, Carla Maria Lins de
Barbosa, Andrezza M.
Sarmento-Neto, José F.
Jesus, Itamar C. G.
Vasconcelos, Valério M. N.
Gomes, Fagner D. L.
Lara, Aline
Cruz, Jader S.
Batinic-Haberle, Ines
Rebouças, Júlio S.
Guatimosim, Silvia
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-03-21
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
Background.
Cardiomyopathies remain among the leading causes of death worldwide, despite all efforts and important advances in the development of cardiovascular therapeutics, demonstrating the need for new solutions.
Herein, we describe the effects of the redox-active therapeutic Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin, AEOL10113, BMX-010 (MnTE-2-PyP5+), on rat heart as an entry to new strategies to circumvent cardiomyopathies.
Methods.
Wistar rats weighing 250-300 g were used in both in vitro and in vivo experiments, to analyze intracellular Ca2+ dynamics, L-type Ca2+ currents, Ca2+ spark frequency, intracellular reactive oxygen species (ROS) levels, and cardiomyocyte and cardiac contractility, in control and MnTE-2-PyP5+-treated cells, hearts, or animals.
Cells and hearts were treated with 20 μM MnTE-2-PyP5+ and animals with 1 mg/kg, i.p.
daily.
Additionally, we performed electrocardiographic and echocardiographic analysis.
Results.
Using isolated rat cardiomyocytes, we observed that MnTE-2-PyP5+ reduced intracellular Ca2+ transient amplitude, without altering cell contractility.
Whereas MnTE-2-PyP5+ did not alter basal ROS levels, it was efficient in modulating cardiomyocyte redox state under stress conditions; MnTE-2-PyP5+ reduced Ca2+ spark frequency and increased sarcoplasmic reticulum (SR) Ca2+ load.
Accordingly, analysis of isolated perfused rat hearts showed that MnTE-2-PyP5+ preserves cardiac function, increases SR Ca2+ load, and reduces arrhythmia index, indicating an antiarrhythmic effect.
In vivo experiments showed that MnTE-2-PyP5+ treatment increased Ca2+ transient, preserved cardiac ejection fraction, and reduced arrhythmia index and duration.
MnTE-2-PyP5+ was effective both to prevent and to treat cardiac arrhythmias.
Conclusion.
MnTE-2-PyP5+ prevents and treats cardiac arrhythmias in rats.
In contrast to most antiarrhythmic drugs, MnTE-2-PyP5+ preserves cardiac contractile function, arising, thus, as a prospective therapeutic for improvement of cardiac arrhythmia treatment.
American Psychological Association (APA)
Barbosa, Andrezza M.& Sarmento-Neto, José F.& Menezes-Filho, José Evaldo Rodrigues de& Jesus, Itamar C. G.& Souza, Diego Santos de& Vasconcelos, Valério M. N.…[et al.]. 2020. Redox-Active Drug, MnTE-2-PyP5+, Prevents and Treats Cardiac Arrhythmias Preserving Heart Contractile Function. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-15.
https://search.emarefa.net/detail/BIM-1204630
Modern Language Association (MLA)
Barbosa, Andrezza M.…[et al.]. Redox-Active Drug, MnTE-2-PyP5+, Prevents and Treats Cardiac Arrhythmias Preserving Heart Contractile Function. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-15.
https://search.emarefa.net/detail/BIM-1204630
American Medical Association (AMA)
Barbosa, Andrezza M.& Sarmento-Neto, José F.& Menezes-Filho, José Evaldo Rodrigues de& Jesus, Itamar C. G.& Souza, Diego Santos de& Vasconcelos, Valério M. N.…[et al.]. Redox-Active Drug, MnTE-2-PyP5+, Prevents and Treats Cardiac Arrhythmias Preserving Heart Contractile Function. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-15.
https://search.emarefa.net/detail/BIM-1204630
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1204630