Research Article
Redox-Active Drug, MnTE-2-PyP
5+
, Prevents and Treats Cardiac
Arrhythmias Preserving Heart Contractile Function
Andrezza M. Barbosa,
1,2
José F. Sarmento-Neto ,
3
José E. R. Menezes Filho,
4
Itamar C. G. Jesus,
5
Diego S. Souza,
4
Valério M. N. Vasconcelos,
1
Fagner D. L. Gomes,
1
Aline Lara,
1
Juliana S. S. Araújo,
2,6
Sandra S. Mattos,
2
Carla M. L. Vasconcelos ,
4
Silvia Guatimosim,
5
Jader S. Cruz,
7
Ines Batinic-Haberle,
8
Demetrius A. M. Araújo ,
1
Júlio S. Rebouças ,
3
and Enéas R. Gomes
1,2
1
Department of Biotechnology, Federal University of Paraiba, Joao Pessoa, Brazil
2
Heart Circle, Recife, Brazil
3
Department of Chemistry, Federal University of Paraiba, Joao Pessoa, Brazil
4
Department of Physiology, Federal University of Sergipe, Aracaju, Brazil
5
Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil
6
Department of Public Health, Federal University of Paraiba, Joao Pessoa, Brazil
7
Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, Brazil
8
Department of Radiation Oncology, Duke University School of Medicine, Durham, NC 27710, USA
Correspondence should be addressed to Enéas R. Gomes; eneasricardo@yahoo.com.br
Received 12 July 2019; Accepted 11 January 2020; Published 21 March 2020
Guest Editor: Adrian Doroszko
Copyright © 2020 Andrezza M. Barbosa et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
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-PyP
5+
), 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 Ca
2+
dynamics, L-type Ca
2+
currents, Ca
2+
spark frequency,
intracellular reactive oxygen species (ROS) levels, and cardiomyocyte and cardiac contractility, in control and MnTE-2-PyP
5+
-
treated cells, hearts, or animals. Cells and hearts were treated with 20 μM MnTE-2-PyP
5+
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-PyP
5+
reduced intracellular Ca
2+
transient amplitude, without altering cell contractility. Whereas
MnTE-2-PyP
5+
did not alter basal ROS levels, it was efficient in modulating cardiomyocyte redox state under stress conditions;
MnTE-2-PyP
5+
reduced Ca
2+
spark frequency and increased sarcoplasmic reticulum (SR) Ca
2+
load. Accordingly, analysis of
isolated perfused rat hearts showed that MnTE-2-PyP
5+
preserves cardiac function, increases SR Ca
2+
load, and reduces
arrhythmia index, indicating an antiarrhythmic effect. In vivo experiments showed that MnTE-2-PyP
5+
treatment increased
Ca
2+
transient, preserved cardiac ejection fraction, and reduced arrhythmia index and duration. MnTE-2-PyP
5+
was effective
both to prevent and to treat cardiac arrhythmias. Conclusion. MnTE-2-PyP
5+
prevents and treats cardiac arrhythmias in rats. In
contrast to most antiarrhythmic drugs, MnTE-2-PyP
5+
preserves cardiac contractile function, arising, thus, as a prospective
therapeutic for improvement of cardiac arrhythmia treatment.
Hindawi
Oxidative Medicine and Cellular Longevity
Volume 2020, Article ID 4850697, 15 pages
https://doi.org/10.1155/2020/4850697