Efecto de tratamientos antiparasitarios, con bajas dosis de Benznidazol y sus nuevas nanoformulaciones en la infección crónica murina por Trypanosoma cruzi Nicaragua y T. cruzi (Sylvio-X-10/4)

We studied the effect of low doses of BNZ in different models of mice with chronic infection by Trypanosoma cruzi Nicaragua, with two schedules of administration of BNZ, continuous and intermittent and combined with ALO. The objective was to reduce the total dose of drug administered without losing...

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Autor principal: Rial, Marcela Silvina
Otros Autores: Nowicki, Cristina
Formato: Tesis doctoral acceptedVersion
Lenguaje:Español
Publicado: Facultad de Farmacia y Bioquímica 2019
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Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_2963
http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_2963.dir/2963.PDF
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Sumario:We studied the effect of low doses of BNZ in different models of mice with chronic infection by Trypanosoma cruzi Nicaragua, with two schedules of administration of BNZ, continuous and intermittent and combined with ALO. The objective was to reduce the total dose of drug administered without losing efficacy. We observed reduction of parasitemia by qPCR, serology by ELISA and myocardial damage by histopathology and electrocardiography.\nIn addition, we evaluated the effect of new nanoformulations of BNZ that were not toxic for the cells nor generated hemolysis, managed to lyse trypomastigotes, inhibited the growth of intracellular amastigotes and produced ROS in Vero cells. In mice with acute and chronic infection, BNZ-nps achieved 100% survival rate, reduced the parasitic load to undetectable levels and significantly decreased the levels of antibodies specific for T. cruzi. The electrocardiograms showed the normalization of the conduction alterations, the levels of inflammation of the cardiac tissue were reduced and the progression of the fibrosis was inhibited.\nTherefore, intermittent treatment could be considered a scheme with less drug accumulation and equally effective on cardiac pathology, and BNZ-nps could reduce the frequency of administration and the side effects evidenced in patients.\n