ABC | Volume 114, Nº6, June 2020

Original Article Yurre et al. Evaluation of the cardiac effects of WSMoL Arq Bras Cardiol. 2020; 114(6):1029-1037 Figure 2 – WSMoL did not impair in vivo or in vitro cardiac electrical activity. Representative in vivo ECG recordings of (A) CNTRL and (B) WSMoL groups. (C) PR, (D) RR, (E) QRS and (F) QJ intervals summarized the data obtained after 21 days of WSMoL treatment (CNTRL n = 7 mice; 2,034 measurements and WSMoL n = 7 mice; 2,038 measurements). Each dot represents individual values and lines represent mean values. Representative in vitro recordings of ventricular action potential of (G) CNTRL and (H) WSMoL groups are showed. The effect of WSMoL treatment on action potential duration at (I) 30% and (J) 90% repolarization are summarized (CNTRL n = 5 hearts; 483 measurements, and WSMoL n = 4 hearts; 545 measurements). Each dot represents individual measurements and lines represent mean values. Comparisons between groups were performed using unpaired Student’s t test, and data that did not show Gaussian distribution (Kolmogorov-Smirnov test) were compared by the Mann Whitney test. ○: CNTRL mice; ●: WSMoL mice. The results are shown as mean ± SD for data with Gaussian distribution and as median and interquartile range for data with non-Gaussian distribution. CNTRL WsMoL CNTRL 20 ms 20 ms 100 ms 100 ms 50 mV 50 mV WsMoL CNTRL QRS (ms) PR (ms) RR (ms) APD 30 (ms) APD 90 (ms) QJ (ms) CNTRL CNTRL WsMoL WsMoL WsMoL CNTRL WsMoL CNTRL WsMoL CNTRL WsMoL 20 10 0 20 25 15 5 10 0 15 5 10 0 120 40 80 0 6 2 4 0 30 40 50 C D E A B G H I J F 25 0 50 75 100 There is a belief that the natural origin of a product guarantees its safety to humans. However, some natural compounds may exert toxic effects, including on the cardiac level. For example, the alkaloid aconitine, an ingredient of Fuzi (a traditional Chinese medicine), was pointed out as the cause of bidirectional ventricular tachycardia. 38 It is also well known that several antibiotics are able to block hERG potassium channels, prolonging the QT interval and the APD. 39-41 Guo et al. 42 observed a prolongation of APD using erythromycin in neonatal mouse ventricular myocytes. Zhang M. et al. 43 also showed that azithromycin, when administered in guinea pigs, caused significant prolongations of APD 50 and APD 90 . Accordingly, we evaluated the effects of WSMoL treatment on the cardiac electric activity both in vivo and ex vivo , in mice, observing that it was cardiologically safe. Another effect observed in some antibiotics is the impairment of left ventricular function and structure, as observed by Zhang M. et al. 43 . Furthermore, some studies have shown that antibiotics and other natural compounds can impair mitochondrial function. 44,45 However, after 21 days of WSMoL treatment, we observed that left ventricular function and mitochondrial function were preserved. Conclusion The data presented here indicate that the administration of WSMoL by gavage did not have cardiotoxic effects on mice treated for 21 days. These results contribute to the safety evaluation of the use of M. oleifera seeds to treat water, since this lectin is present in the preparation employed by some populations to this end. Acknowledgements The authors express their gratitude to the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for financial support and investigator research grants (THN, PMGP, EHM). We are also grateful to the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Financial Code: 001) and the Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco (FACEPE; APQ-0661- 2.08/15) for financial support. JDFS would like to thank FACEPE (IBPG-0841-2.08/15) for graduate scholarship and CAPES for mobility assistance (88881.068531/2014-01; PROCAD/2013 - 88887.124150/2014-00). In addition, the authors want to thanks Professor Ariel Escobar fromUniversity of California who gave us support to record and analyze the 1033

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