Although
suramin (Sur) is suggested as a potential
drug candidate in the management of
Chagas disease, this issue has not been objectively tested. In this study, we examined the applicability of concomitant treatment with
benznidazole (Bz) and
suramin in mice infected with a virulent strain of Trypanosoma cruzi. Eighty 12-week-old male C57BL/6 mice were equally randomized in eight groups: (i) noninfected mice (negative control) and mice infected with T. cruzi Y strain receiving (ii) no treatment (positive control), (iii) Bz, 100 mg/kg of
body weight per day, (iv) Sur, 20 mg/kg/day, and (v to viii) Sur, 20 mg/kg/day, combined with Bz, 100, 50, 25, or 5 mg/kg/day. Bz was administered by gavage, and Sur was administered intraperitoneally. Sur dramatically increased the
parasitemia, cardiac content of parasite
DNA,
inflammation, oxidative tissue damage, and mortality. In response to high parasitic load in cardiac tissue, Sur stimulated the immune system in a manner typical of the acute phase of
Chagas disease, increasing tissue levels of
gamma interferon (IFN-γ) and
tumor necrosis factor alpha (TNF-α) and inducing a preferential
IgG2a anti-T. cruzi serum pattern. When Sur and Bz were combined, the
infection severity was attenuated, showing a dose-dependent Bz response. Sur
therapy had a more harmful effect on the host than on the parasite and reduced the efficacy of Bz against T. cruzi
infection. Considering that Sur drastically reinforced the
infection evolution, potentiating the inflammatory process and the severity of cardiac lesions, the in vivo findings contradicted the in vitro
anti-T. cruzi potential described for this
drug.