Nitazoxanide modulates inflammation but fails to control parasitemia in experimental Trypanosoma cruzi infection.

Chagas disease, caused by Trypanosoma cruzi, currently lacks effective therapies that target both bloodstream and muscle-resident parasites. Given the limitations of current treatments, such as benznidazole and nifurtimox, complementary chemical strategies are crucial not only for parasite elimination but also for modulating host inflammatory responses. In this study, female C57BL/6 mice were infected with the Y strain of T. cruzi (DTU TcII) and treated orally with nitazoxanide (NTZ) twice daily for 10 days at doses ranging from 100 to 1200 mg/kg. We evaluated parasitemia, survival rates, serum levels of inflammatory mediators (TNF, IL-10, IL-17, and CCL2), liver enzyme activities (AST, ALT), and leukocyte infiltration in cardiac tissue. NTZ modulated inflammatory responses in a dose-dependent manner. Moderate doses (200 to 600 mg/kg) significantly reduced serum levels of TNF, IL-10, and IL-17, and decreased cardiac leukocyte infiltration. However, higher doses of NTZ (800 to 1200 mg/kg) increased parasitemia and AST levels, without altering ALT. Although NTZ attenuated inflammation without inducing significant hepatotoxicity, it failed to effectively control parasitemia when compared with untreated infected controls. These findings suggest that while NTZ may serve as a promising adjunctive therapy to modulate inflammatory responses in Chagas disease, it is insufficient as a monotherapy for parasite clearance.