dc.contributor | López Casillas, Marcos | |
dc.creator | Rodríguez Avila, Yudy A. | |
dc.date.accessioned | 2018-11-23T20:32:54Z | |
dc.date.available | 2018-11-23T20:32:54Z | |
dc.date.created | 2018-11-23T20:32:54Z | |
dc.date.issued | 2017-10-15 | |
dc.identifier | T 86.17 R762c | |
dc.identifier | https://repositorio.udes.edu.co/handle/001/640 | |
dc.description.abstract | La cardiomiopatía chagásica es el evento más serio y más frecuente de la enfermedad de chagas. La invasión por T. cruzi genera alteraciones en la función mitocondrial del cardiomiocito que se traducen a pérdida del potencial de membrana mitocondrial, generación de especies reactivas de oxígeno ROS y alteración en el balance antioxidante, contribuyendo a un desequilibrio metabólico y oxidativo en el miocardio chagásico. Nosotros evaluamos los efectos de nitróxidos miméticos de SOD (SG1 y Mito-SG1) y del tratamiento de referencia BZN sobre la capacidad pro-oxidante, la bioenergética celular e infectividad de cardiomiocitos humanos AC16 infectados con T. cruzi. Materiales y Métodos: La citotoxicidad celular fue realizada por el ensayo MTT. La infectividad parasitaria fue determinada por citometría de flujo, utilizando el reactivo CFSE. La bioenergética celular se determinó con el sistema Seahorse XFe-24 Analyzer y la producción de ROS Mitocondrial por MitoSOX™ Red. Resultados: El CC50 para SG1 fue de 4790 μM, para Mito-SG1 de 5,0 μM. BZN y Mito-SG1 tuvieron efectos en la disminución de la tasa de infectividad de los cardiomiocitos humanos. Se obtuvo diferencias significativas en los efectos pro-oxidantes de los cardiomiocitos tratados con BZN. Se observaron cambios importantes estadísticamente en los parámetros de respiración basal, producción de ATP, protón leak y respiración máxima en los cardiomiocitos infectados con T. cruzi. La capacidad de reserva respiratoria disminuyo en los cardiomiocitos infectados y sometidos a los tratamientos con BZN, SG1 y Mito-SG1. Conclusiones: El cardiomiocito humano sufre perturbaciones metabólicas tempranas que involucran cambios en el consumo de oxígeno y perfil bioenergético hacia la utilización de la vía glucolítica. La disminución de la infectividad en los cardiomiocitos tratados con Mito-SG1, es un hallazgo que permite realizar estudios futuros con el fin de determinar posibles efectos antiparásitarios del mitocompuesto. | |
dc.description.abstract | Chagasic cardiomyopathy is the most serious and frequent event of this disease. Previous studies have shown that infection by T. cruzi induces alterations in mitochondrial function of cardiomyocytes that result in loss of mitochondrial membrane potential, generation of reactive species ROS and alteration in the antioxidant balance, contributing to a metabolic and oxidative imbalance in the chagasic myocardium. We evaluated the effects of SOD mimetic mitochondria targeted and non-targeted nitroxides compounds SG1 and Mito-SG1 and the reference treatment on pro-oxidant capacity, cellular bioenergetics and infectivity of human cardiomyocytes infected with T. cruzi. Materials and methods: Cellular cytotoxicity was determined by the MTT assay. Flow cytometry determined infectivity, using the CFSE reagent for labeling of infective tripomastigotes. The bioenergetics and mitochondrial function was determined with Seahorse XFe-24 Analyzer, and production of superoxide by MitoSOX™ Red. Results: The CC50 was determined ≥ 4790μM for SG1, for Mito-SG1 of 5,0μM. Significant differences were found in the pro-oxidant effects of the cardiomyocytes treated with BZN and BZN more infection. Statistically significant changes were observed in the parameters of Basal respiration, ATP production, Proton leak and Maximal respiration in cardiomyocytes infected with T. cruzi. Spare Respiratory Capacity decreased in cardiomyocytes under treatment with BZN, SG1 and Mito-SG1 and T. cruzi infection. BZN and Mito-SG1 had effects in decreasing the infectivity rate of human cardiomyocytes. Conclusions: The AC16 human cardiomyocyte presents early metabolic disturbances that involve changes in oxygen consumption and bioenergetic profile towards the use of the glycolytic pathway. The decrease in infectivity in cardiomyocytes treated with Mito-SG1 is a finding that allows for future studies to determine the possible antiparasitic effects of this compound. | |
dc.language | spa | |
dc.publisher | Bucaramanga : Universidad de Santander, 2017 | |
dc.publisher | Facultad Ciencias de la Salud | |
dc.publisher | Maestría en Investigación en enfermedades Infecciosas | |
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dc.rights | info:eu-repo/semantics/openAccess | |
dc.rights | Atribución-NoComercial 4.0 Internacional (CC BY-NC 4.0) | |
dc.rights | https://creativecommons.org/licenses/by-nc/4.0/ | |
dc.rights | Derechos Reservados - Universidad de Santander, 2017 | |
dc.title | Cardioprotección por antioxidantes mitocondriales en cardiomiocitos humanos infectados con Trypanosoma cruzi | |
dc.type | Trabajo de grado - Maestría | |