Cardiovasc Toxicol. 2021 Oct 16; doi: 10.1007/s12012-021-09702-w. Epub 2021 Oct 16.

Comparative Therapeutic Potential of Cardioactive Glycosides in Doxorubicin Model of Heart Failure.

Cardiovascular toxicology

Raquel da Silva Ferreira, Paula Bretas Ullmann Fernandes, Jéssica Pereira Oliveira da Cruz, Françoise Louanne Araújo Silva, Marthin Raboch Lempek, Gioavanni Naves Canta, Júlio César Cambraia Veado, Matheus Matioli Mantovani, Ana Flávia Machado Botelho, Marília Martins Melo

PMID: 34655414 DOI: 10.1007/s12012-021-09702-w

Abstract

In the present study, we investigated the cardioactive glycosides oleandrin and ouabain, and compared them to digoxin in a model of cardiotoxicity induced by doxorubicin. Adult rats were distributed into four experimental groups. Each group was challenged with a single intraperitoneal application of doxorubicin at a dose of 12 mg/kg. Then, they were treated with saline solution and the glycosides oleandrin, ouabain, and digoxin at a dose of 50 µg/kg, for 7 days. They underwent echocardiography, electrocardiography, hematologic, biochemical tests, and microscopic evaluation of the heart. All animals presented congestive heart failure, which was verified by a reduction in the ejection fraction. Oleandrin and digoxin were able to significantly reduce (p < 0.05) the eccentric remodeling caused by doxorubicin. Oleandrin and digoxin were significantly lower (p < 0.05) than the control group in maintaining systolic volume and left ventricular volume in diastole. Other parameters evaluated did not show significant statistical differences. All animals showed an increase in erythrocyte count, and an increase in the duration of the QRS complex on the ECG and myocardial necrosis at the histopathological analysis. It is concluded that the glycosides oleandrin, ouabain, and digoxin in the used dosage do not present therapeutic potential for the treatment of congestive heart failure caused by doxorubicin.

© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Keywords: Cardenolides; Cardiac remodeling; Digitalis; Inotropism

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