ABC | Volume 114, Nº6, June 2020

Original Article Evaluation of the Cardiac Effects of a Water-Soluble Lectin (Wsmol) from Moringa Oleifera Seeds Ainhoa Rodríguez de Yurre, 1 * José Dayvid Ferreira da Silva, 2* M arília Kalinne da Silva Torres, 2 E duarda Lopes Martins, 1 Isalira Peroba Ramos, 1 Wênio Sandoval Filho Lima da Silva, 2 Jéssica da Silva Sarpa, 2 Caio César da Silva Guedes, 2 Thiago Henrique Napoleão, 2 Luana Cassandra Breitenbach Barroso Coelho, 2 Patrícia Maria Guedes Paiva, 2 Emiliano Medei 1 Universidade Federal do Rio de Janeiro, 1 Rio de Janeiro, RJ – Brazil Universidade Federal de Pernambuco, 2 Recife, PE – Brazil *These authors contributed equally to this work Mailing Address: Emiliano Medei • Universidade Federal do Rio de Janeiro – Av. Carlos Chagas Filho, 373, CCS, Bloco G. Postal Code 21941-901, Rio de Janeiro, RJ – Brazil E-mail: emedei70@biof.ufrj.br Manuscript received February 20, 2018, revised manuscript May 04, 2019, accepted June 23, 2019 DOI: https://doi.org/10.36660/abc.20190071 Abstract Background: Moringa oleifera seeds, which are used for water clarification, contain a lectin named WSMoL which has shown in vitro antibacterial and immunomodulatory activity. Due to their nutritional value and therapeutic potential, the leaves and seeds of this tree are eaten in some communities. Some plant lectins are non-toxic to mammals, but others have been reported to be harmful when ingested or administered by other means. Objective: As one of the steps needed to define the safety of WSMoL, we evaluated possible cardiotoxic effects of this purified protein. Methods: WSMoL was administered for 21 consecutive days to mice by gavage. Electrophysiological, mechanical, and metabolic cardiac functions were investigated by in vivo and ex vivo electrocardiographic recordings, nuclear magnetic resonance, and high-resolution respirometry. Results: The treatment with WSMoL did not induce changes in blood glucose levels or body weight in comparison with control group. Moreover, the heart weight/body weight and heart weight/tibia length ratios were similar in both groups. Lectin ingestion also did not modify glucose tolerance or insulin resistance. No alterations were observed in electrocardiographic parameters or cardiac action potential duration. The heart of mice from the control andWSMoL groups showed preserved left ventricular function. Furthermore, WSMoL did not induce changes in mitochondrial function (in all cases, p > 0.05). Conclusions: The administration of WSMoL demonstrated a cardiac safety profile. These results contribute to the safety evaluation of using M. oleifera seeds to treat water, since this lectin is present in the preparation employed by some populations to this end. (Arq Bras Cardiol. 2020; 114(6):1029-1037) Keywords: Moringa Oleífera (WSMoL), Lectins, Glycosides; Carbohydrates; Heart; Water Security; Mice. Introduction Moringa oleifera Lamarck (Moringaceae) is a tree that is native to the south Himalaya region, widely cultivated on Asia and throughout the tropics mainly due to its use for water clarification. It has been employed in traditional medicine, as well as in food, cosmetic, and pharmaceutical industries, 1,2 and it is also used to treat different diseases, such as cancer and chronic and infectious diseases. 3,4 A water-soluble lectin isolated from the seeds of M. oleifera (WSMoL) has shown insecticidal activity, 5-7 and in vitro studies demonstrated its antibacterial activity against corrosive and pathogenic bacteria. 8-10 WSMoL demonstrated in vitro anti- inflammatory activity on lipopolysaccharide-stimulated murine macrophages, 11 and it was able to activate human lymphocytes from peripheral blood mononuclear cell cultures, showing an immunomodulatory effect. 12 It has also been proven that WSMoL is one of the coagulant proteins found in M. oleifera seeds 8,13 and it is able to reduce the turbidity and ecotoxicity of water samples collected from a polluted stream. 14 It is well demonstrated that many antibiotics and some classes of anti-inflammatory drugs are usually associated with cardiotoxic effects. 15,16 The injurious events of these drugs in the cardiovascular system include the occurrence of heart failure with systolic ventricular dysfunction, arrhythmias, andmyocardial ischemia. 17 Classically, as a consequence of cardiotoxicity, changes on the electrocardiogram (ECG) can be observed, such as QT interval prolongation, which has been observed in patients who have used several classes of antimicrobials, including macrolides and fluoroquinolones. 18-20 Among macrolides, intravenous administration of erythromycin presents the greatest risk. It increases the QT interval, and fatal arrhythmias have been reported when it was used alone or in combination with other QT-prolonging drugs. 16 Thus, protection of cardiac function is currently a constant challenge for the pharmaceutical industry, regulatory authorities, and physicians facing adverse clinical reactions to various therapeutic agents in clinical practice. 1029