Combined treatment of benznidazole with an electrolyzed oxidizing water against Trypanosoma cruzi on immunological and anatomopathological features in a murine model of Chagas disease

Vollständiger Abstract

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Background The rising reports of drug resistance in Trypanosoma cruzi strains and the high toxicity of current treatments necessitate the exploration of therapeutic alternatives for Chagas disease (ChD). This study evaluated the efficacy of combining benznidazole (BZN) with electrolyzed oxidizing water (EOW) to assess its impact on clinical parameters, immune response, and tissue integrity. Methods Forty female BALB/c mice were infected intraperitoneally with 150 blood trypomastigotes of the T. cruzi H8 strain. Subjects were divided into eight experimental groups across two independent trials. We monitored parasitemia, weight fluctuations, and survival. Humoral response (IgG and subclasses) and cellular profiles (pro-inflammatory and anti-inflammatory cytokines) were determined via ELISA and flow cytometry, respectively. Histopathological and anatomopathological assessments of target organs were conducted at necropsy. Results The BZN+EOW regimen achieved a 99.2% reduction in parasitemia and a 100% survival rate. Although the combination did not statistically surpass BZN monotherapy in absolute parasite clearance, it promoted significant clinical recovery, with weight gain exceeding 50% compared to the untreated infected group. Immunologically, the combination triggered a robust Th1-type immune profile response during the acute phase (40 dpi). By 365 dpi, this response shifted toward a more counterbalanced Th1/Th2 immune microenvironment, correlating with minimal and non-severe histopathological alterations in cardiac and skeletal tissues. Discussion These findings suggest that BZN+EOW therapy preserved the trypanocidal efficacy observed with the monotherapy, yet it presented the added advantage of subtly refining the inflammatory landscape in the chronic phase. This balanced immune response could help prevent severe chronic tissue damage, offering a promising adjunct approach to improve the prognosis for ChD.