Purinergic Antagonist Suramin Aggravates Myocarditis and Increases Mortality by Enhancing Parasitism, Inflammation, and Reactive Tissue Damage in Trypanosoma cruzi-Infected Mice

Abstract EN

Suramin (Sur) acts as an ecto-NTPDase inhibitor in Trypanosoma cruzi and a P2-purinoceptor antagonist in mammalian cells.

Although the potent antitrypanosomal effect of Sur has been shown in vitro, limited evidence in vivo suggests that this drug can be dangerous to T.

cruzi-infected hosts.

Therefore, we investigated the dose-dependent effect of Sur-based chemotherapy in a murine model of Chagas disease.

Seventy uninfected and T.

cruzi-infected male C57BL/6 mice were randomized into five groups: SAL = uninfected; INF = infected; SR5, SR10, and SR20 = infected treated with 5, 10, or 20 mg/kg Sur.

In addition to its effect on blood and heart parasitism, the impact of Sur-based chemotherapy on leucocytes myocardial infiltration, cytokine levels, antioxidant defenses, reactive tissue damage, and mortality was analyzed.

Our results indicated that animals treated with 10 and 20 mg/kg Sur were disproportionally susceptible to T.

cruzi, exhibiting increased parasitemia and cardiac parasitism (amastigote nests and parasite load (T.

cruzi DNA)), intense protein, lipid and DNA oxidation, marked myocarditis, and mortality.

Animals treated with Sur also exhibited reduced levels of nonprotein antioxidants.

However, the upregulation of catalase, superoxide dismutase, and glutathione-S-transferase was insufficient to counteract reactive tissue damage and pathological myocardial remodeling.

It is still poorly understood whether Sur exerts a negative impact on the purinergic signaling of T.

cruzi-infected host cells.

However, our findings clearly demonstrated that through enhanced parasitism, inflammation, and reactive tissue damage, Sur-based chemotherapy contributes to aggravating myocarditis and increasing mortality rates in T.

cruzi-infected mice, contradicting the supposed relevance attributed to this drug for the treatment of Chagas disease.