Metallothionein-1 and nitric oxide expression are inversely correlated in a murine model of Chagas disease

Chagas disease, caused by Trypanosoma cruzi, represents an endemicamong Latin America countries. The participation of free radicals, especially nitricoxide (NO), has been demonstrated in the pathophysiology of seropositive individualswith T. cruzi. In Chagas disease, increased NO contributes to thedevelopment of cardiomyopathy and megacolon. Metallothioneins (MTs) are efficientfree radicals scavengers of NO in vitro and in vivo. Here, we developed a murinemodel of the chronic phase of Chagas disease using endemic T. cruziRyCH1 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-NAMEtreated and non-infected vehicle-treated. We determined blood parasitaemia and NOlevels, the extent of parasite nests in tissues and liver MT-I expression levels. Itwas 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 skeletalmuscle with decreased blood NO levels at day 135 post infection. This affect wasnegatively correlated with an increase of MT-I expression (r = -0.8462, p <0.0001). In conclusion, we determined that in Chagas disease, an unknown inhibitorymechanism reduces MT-I expression, allowing augmented NO levels.