Branquinho, Renata TupinambáRoy, JérômeFarah, CharlotteGarcia, Giani MartinsAimond, FranckGuennec, Jean Yves LeGuimarães, Dênia Antunes SaúdeGuimarães, Andrea GrabeMosqueira, Vanessa Carla FurtadoLana, Marta deRichard, Sylvain2017-08-302017-08-302017BRANQUINHO, R. T. et al. Biodegradable polymeric nanocapsules prevent cardiotoxicity of anti-trypanosomal lychnopholide. Scientific Reports, v. 7, p. 44998, 2017. Disponível em: <https://www.nature.com/articles/srep44998>. Acesso em: 29 ago. 2017.2045-2322http://www.repositorio.ufop.br/handle/123456789/8588Chagas disease is a neglected parasitic disease caused by the protozoan Trypanosoma cruzi. New antitrypanosomal options are desirable to prevent complications, including a high rate of cardiomyopathy. Recently, a natural substance, lychnopholide, has shown therapeutic potential, especially when encapsulated in biodegradable polymeric nanocapsules. However, little is known regarding possible adverse effects of lychnopholide. Here we show that repeated-dose intravenous administration of free lychnopholide (2.0 mg/kg/day) for 20 days caused cardiopathy and mortality in healthy C57BL/6 mice. Echocardiography revealed concentric left ventricular hypertrophy with preserved ejection fraction, diastolic dysfunction and chamber dilatation at end-stage. Single cardiomyocytes presented altered contractility and Ca2+ handling, with spontaneous Ca2+ waves in diastole. Acute in vitro lychnopholide application on cardiomyocytes from healthy mice also induced Ca2+ handling alterations with abnormal RyR2-mediated diastolic Ca2+ release. Strikingly, the encapsulation of lychnopholide prevented the cardiac alterations induced in vivo by the free form repeated doses. Nanocapsules alone had no adverse cardiac effects. Altogether, our data establish lychnopholide presented in nanocapsule form more firmly as a promising new drug candidate to cure Chagas disease with minimal cardiotoxicity. Our study also highlights the potential of nanotechnology not only to improve the efficacy of a drug but also to protect against its adverse effects.en-USabertoArtigo publicado em periodicoThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Fonte: o próprio artigo.https://doi.org/10.1038/srep44998