Abstract

During Trypanosoma cruzi infection, oxidative stress is considered a contributing factor for dilated cardiomyopathy development. In this study, the effects of astaxanthin (ASTX) were evaluated as an alternative drug treatment for Chagas disease in a mouse model during the acute infection phase, given its anti-inflammatory, immunomodulating, and anti-oxidative properties. ASTX was tested in vitro in parasites grown axenically and in co-culture with Vero cells. In vivo tests were performed in BALB/c mice (4–6 weeks old) infected with Trypanosoma cruzi and supplemented with ASTX (10 mg/kg/day) and/or nifurtimox (NFMX; 100 mg/kg/day). Results show that ASTX has some detrimental effects on axenically cultured parasites, but not when cultured with mammalian cell monolayers. In vivo, ASTX did not have any therapeutic value against acute Trypanosoma cruzi infection, used either alone or in combination with NFMX. Infected animals treated with NFMX or ASTX/NFMX survived the experimental period (60 days), while infected animals treated only with ASTX died before day 30 post-infection. ASTX did not show any effect on the control of parasitemia; however, it was associated with an increment in focal heart lymphoplasmacytic infiltration, a reduced number of amastigote nests in cardiac tissue, and less hyperplasic spleen follicles when compared to control groups. Unexpectedly, ASTX showed a negative effect in infected animals co-treated with NFMX. An increment in parasitemia duration was observed, possibly due to ASTX blocking of free radicals, an anti-parasitic mechanism of NFMX. In conclusion, astaxanthin is not recommended during the acute phase of Chagas disease, either alone or in combination with nifurtimox.

Highlights

  • Chagas disease is a zoonotic health concern in Latin America caused by Trypanosoma cruzi, with an estimated 6–7 million people infected

  • Considering the results reported by Wen et al [51], who found that PBN, a synthetic antioxidant, used in Sprague Dawley rats infected with T. cruzi, did not decrease parasite load during the acute phase of infection, it could be concluded that the use of antioxidants is not indicated during this phase of Chagas disease

  • Our results showed statistical differences between serum MDA from infected (G3 and G4 groups) and non-infected animals (G5–G8 groups) (Fig. 6)

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Summary

Introduction

Chagas disease is a zoonotic health concern in Latin America caused by Trypanosoma cruzi, with an estimated 6–7 million people infected. The drugs available for the treatment of Trypanosoma cruzi infection in institutional health systems in Latin America are nifurtimox and benznidazole. These drugs have limited therapeutic value since they are effective only during the acute stages of the disease, and because these drugs may induce severe side effects in people undergoing long-term treatment [10, 50]. Resistance to NFMX and benznidazole has been reported in parasites of different genotypes in endemic zones [9] These therapeutic drawbacks leave people of all ages at risk [46, 47], and new strategies should be studied if an effective treatment is to be found

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