title: Metallothionein-1 and nitric oxide expression are inversely correlated in a murine model of Chagas disease.
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.
authors.affiliation: Facultad de Medicina, Benemérita Universidad Autónoma de Puebla, Puebla, México.
authors.forename: Martha Elba
authors.initials: ME
authors.lastname: Gonzalez-Mejia
authors.affiliation: Facultad de Medicina, Benemérita Universidad Autónoma de Puebla, Puebla, México.
authors.forename: Enrique
authors.initials: E
authors.lastname: Torres-Rasgado
authors.affiliation: Laboratorio de Fisiopatología de Enfermedades Crónicas, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Puebla, México.
authors.forename: Leonardo M
authors.initials: LM
authors.lastname: Porchia
authors.affiliation: Laboratorio de Fisiopatología de Enfermedades Crónicas, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Puebla, México.
authors.forename: Hilda Rosas
authors.initials: HR
authors.lastname: Salgado
authors.affiliation: Laboratorio de Fisiopatología de Enfermedades Crónicas, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Puebla, México.
authors.forename: José-Luis
authors.initials: JL
authors.lastname: Totolhua
authors.affiliation: Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados, Unidad Zacatenco, México DF, México.
authors.forename: Arturo
authors.initials: A
authors.lastname: Ortega
authors.affiliation: Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados, Unidad Zacatenco, México DF, México.
authors.forename: Luisa Clara Regina
authors.initials: LC
authors.lastname: Hernández-Kelly
authors.affiliation: Facultad de Medicina, Benemérita Universidad Autónoma de Puebla, Puebla, México.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Ruiz-Vivanco
authors.affiliation: Facultad de Medicina, Benemérita Universidad Autónoma de Puebla, Puebla, México.
authors.forename: Blanca G
authors.initials: BG
authors.lastname: Báez-Duarte
authors.affiliation: Facultad de Medicina, Benemérita Universidad Autónoma de Puebla, Puebla, México.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pérez-Fuentes
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000032:analysis; D014355:Chagas Disease / Q000097:blood* / Q000188:drug therapy; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D006321:Heart / Q000469:parasitology; D008668:Metallothionein / Q000097:blood*; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use; D009569:Nitric Oxide / Q000097:blood*; D018384:Oxidative Stress; D018512:Parasitemia / Q000097:blood / Q000503:physiopathology; D060888:Real-Time Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013997:Time Factors; D014349:Trypanosoma cruzi
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D008668:Metallothionein; D019331:NG-Nitroarginine Methyl Ester