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Although the potent antitrypanosomal effect of Sur has been shown<jats:italic>in vitro<\/jats:italic>, limited evidence<jats:italic>in vivo<\/jats:italic>suggests that this drug can be dangerous to<jats:italic>T. cruzi<\/jats:italic>\u2010infected hosts. Therefore, we investigated the dose\u2010dependent effect of Sur\u2010based chemotherapy in a murine model of Chagas disease. Seventy uninfected and<jats:italic>T. cruzi<\/jats:italic>\u2010infected male C57BL\/6 mice were randomized into five groups: SAL\u2009=\u2009uninfected; INF\u2009=\u2009infected; SR5, SR10, and SR20\u2009=\u2009infected treated with 5, 10, or 20\u2009mg\/kg Sur. In addition to its effect on blood and heart parasitism, the impact of Sur\u2010based 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\u2009mg\/kg Sur were disproportionally susceptible to<jats:italic>T. cruzi<\/jats:italic>, exhibiting increased parasitemia and cardiac parasitism (amastigote nests and parasite load (<jats:italic>T. cruzi<\/jats:italic>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\u2010S\u2010transferase 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<jats:italic>T. cruzi<\/jats:italic>\u2010infected host cells. However, our findings clearly demonstrated that through enhanced parasitism, inflammation, and reactive tissue damage, Sur\u2010based chemotherapy contributes to aggravating myocarditis and increasing mortality rates in<jats:italic>T. cruzi<\/jats:italic>\u2010infected mice, contradicting the supposed relevance attributed to this drug for the treatment of Chagas disease.<\/jats:p>","DOI":"10.1155\/2018\/7385639","type":"journal-article","created":{"date-parts":[[2018,9,30]],"date-time":"2018-09-30T19:32:04Z","timestamp":1538335924000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Purinergic Antagonist Suramin Aggravates Myocarditis and Increases Mortality by Enhancing Parasitism, Inflammation, and Reactive Tissue Damage in<i>Trypanosoma cruzi<\/i>\u2010Infected Mice"],"prefix":"10.1155","volume":"2018","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3186-5328","authenticated-orcid":false,"given":"R\u00f4mulo D.","family":"Novaes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3030-7746","authenticated-orcid":false,"given":"Elizi\u00e1ria C.","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marli C.","family":"Cupertino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7442-8067","authenticated-orcid":false,"given":"Daniel S. 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