Metallothionein-1 and nitric oxide expression are inversely
correlated in a murine model of Chagas disease |
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Authors: | Martha Elba Gonzalez-Mejia Enrique Torres-Rasgado Leonardo M Porchia Hilda Rosas Salgado José-Luis Totolhua Arturo Ortega Luisa Clara Regina Hernández-Kelly Guadalupe Ruiz-Vivanco Blanca G Báez-Duarte Ricardo Pérez-Fuentes |
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Institution: | 1.Facultad de Medicina, Benemérita Universidad Autónoma de Puebla, Puebla, México;2.Laboratorio de Fisiopatología de Enfermedades Crónicas, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Puebla, México;3.Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados, Unidad Zacatenco, México DF,México |
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Abstract: | Chagas disease, caused by Trypanosoma cruzi, represents an endemic
among Latin America countries. The participation of free radicals, especially nitric
oxide (NO), has been demonstrated in the pathophysiology of seropositive individuals
with T. cruzi. In Chagas disease, increased NO contributes to the
development of cardiomyopathy and megacolon. Metallothioneins (MTs) are efficient
free radicals scavengers of NO in vitro and in vivo. Here, we developed a murine
model of the chronic phase of Chagas disease using endemic T. cruzi
RyCH1 in BALB/c mice, which were divided into four groups: infected non-treated
(Inf), infected N-monomethyl-L-arginine treated (Inf L-NAME), non-infected L-NAME
treated and non-infected vehicle-treated. We determined blood parasitaemia and NO
levels, the extent of parasite nests in tissues and liver MT-I expression levels. It
was observed that NO levels were increasing in Inf mice in a time-dependent manner.
Inf L-NAME mice had fewer T. cruzi nests in cardiac and skeletal
muscle with decreased blood NO levels at day 135 post infection. This affect was
negatively correlated with an increase of MT-I expression (r = -0.8462, p <
0.0001). In conclusion, we determined that in Chagas disease, an unknown inhibitory
mechanism reduces MT-I expression, allowing augmented NO levels. |
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Keywords: | metallothionein-I antioxidants nitric oxide L-NAME Chagas disease |
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