Ciencias Exactas y Ciencias de la Salud
Permanent URI for this collectionhttps://hdl.handle.net/11285/551039
Pertenecen a esta colección Tesis y Trabajos de grado de las Maestrías correspondientes a las Escuelas de Ingeniería y Ciencias así como a Medicina y Ciencias de la Salud.
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- Administration of resveratrol and cyclosporine a nanoparticles in a hypoxia/reoxygenation model(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2021-06) Hernández Fontes, Paulina; LOZANO GARCIA, OMAR; 486173; ; Lozano García, Omar; tolmquevedo, emipsanchez; Mayolo Deloisa, Karla P.; Cholula Díaz, Jorge L.; Santillán Zerón, Moíses; Escuela de Medicina y Ciencias de la Salud; Campus Monterrey; García Rivas, Gerardo de JesúsIschemia reperfusion (I/R) injury remains as a neglected therapeutic target, limiting the benefits on morbidity and mortality of early reperfusion therapies. In this work, two separate poly(lactic-co-glycolic) acid (PLGA) nanoparticles incorporating resveratrol (Resv-NPs), a phytoalexin with strong antioxidant potential, and cyclosporine A (CsA-NPs), a pharmacological inhibitor of the mitochondrial permeability transition pore (mPTP), were developed. These molecules present limitations in their pharmacokinetic profiles which obstruct them from being effectively applied as a treatment for I/R injury. In a H9c2 rat cardiomyoblast model of hypoxia/reoxygenation injury, free drugs were compared with their encapsulated counterparts through the assessment of cell viability. In terms of the latter, Resv-NPs appeared to have an equivalent protection than that of free Resv, however, CsA-NPs appeared to widen CsA narrow therapeutic window under the conditions here reported. mPTP opening was assessed through a Ca2+ retention capacity (CRC) assay, where encapsulation appeared to improve Resv-induced inhibition of pore opening at a concentration of 0.1 μM, while both free and encapsulated CsA groups appeared to prevent mPTP opening. The potential in vivo applications of these nanoformulations as well as the perspectives of this work are described.
- The role of the mitochondrial calcium uniporter in the process of arrhythmogenesis in a murine model of acute catecholamine overload(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2020-05-22) Salazar Ramírez, Felipe de Jesús; SALAZAR RAMIREZ, FELIPE DE JESUS; 876167; García Rivas, Gerardo de Jesús; emipsanchez; Alves Figueiredo, Hugo Jorge; Rojas Martínez, Augusto; Ramos Mondragón, Roberto; Escuela de Medicina y Ciencias de la Salud; Campus MonterreySudden cardiac death by fulminant ventricular arrhythmias remains a concern in population with cardiac risk. Recently, the mitochondrion has been implied to be a central player in Ca2+ mishandling, with its dysfunction leading up to arrhythmogenesis. A possible starting event that could lead to most changes seen in cardiac disfunction is mitochondrial Ca2+ overload. The following research study focuses on demonstrating the effects of mitochondrial Ca2+ influx inhibition in arrhythmogenesis. A murine model of acute catecholamine (isoproterenol) overload was treated previously with mitochondrial Ca2+ transport inhibitor Ru360. Ru360 treated mice showed a complete abolishment of ventricular tachycardia and ventricular fibrillation. To characterize the possible mechanisms of action, heart mitochondria were isolated and mitochondrial function was assessed. Mitochondrial Ca2+ transport inhibition preserved mitochondrial function and membrane integrity as demonstrated by a higher respiratory control and calcium retention capacity when compared to isoproterenol-treated mice which appears to be caused by a reduced oxidative stress as a trend to preserve reduced thiol groups was shown. Given the positive results obtained in abolishing ventricular arrhythmias by inhibiting mitochondrial Ca2+ transport, it is precise to continue the characterization of the mechanisms by which this therapy exerts its effects. To fully demonstrate its efficacy and characterize its mechanism of action may lead up to a new therapeutic target and therapy that could set the bases to clinical research in the near future.