Previous studies have demonstrated loss/reduction of
dystrophin in cardiomyocytes in both acute and chronic stages of experimental Trypanosoma cruzi (T. cruzi)
infection in mice. The mechanisms responsible for
dystrophin disruption in the hearts of mice acutely infected with T. cruzi are not completely understood. The present in vivo and in vitro studies were undertaken to evaluate the role of
inflammation in
dystrophin disruption and its correlation with the high mortality rate during acute
infection. C57BL/6 mice were infected with T. cruzi and killed 14, 20 and 26 days post
infection (dpi). The intensity of
inflammation, cardiac expression of
dystrophin, calpain-1, NF-κB, TNF-α, and sarcolemmal permeability were evaluated. Cultured neonatal murine cardiomyocytes were incubated with serum, collected at the peak of
cytokine production and free of parasites, from T. cruzi-infected mice and
dystrophin, calpain-1, and NF-κB expression analyzed.
Dystrophin disruption occurs at the peak of mortality and
inflammation and is associated with increased expression of calpain-1, TNF-α, NF-κB, and increased sarcolemmal permeability in the heart of T. cruzi-infected mice at 20 dpi confirmed by in vitro studies. The peak of mortality occurred only when significant loss of
dystrophin in the hearts of infected animals occurred, highlighting the correlation between
inflammation,
dystrophin loss and mortality.