Theracurmin is a nanoparticle formulation derived from curcumin, a bioactive compound known for its antioxidant and anti-inflammatory properties. Trypanosoma cruzi, the etiological agent of Chagas disease, triggers an intense inflammatory response in mammals and also causes severe tissue damage. To evaluate the immunomodulatory and antiparasitic effects of Theracurmin, Swiss mice were experimentally infected with 103 trypomastigote forms of the Colombian strain of T. cruzi and submitted to daily therapy with 30 mg/kg of Theracurmin. In addition, daily benznidazole therapy (100 mg/kg) was performed as a positive control. We evaluated the systemic and tissue parasitism, the survival and the body mass rate, the release of inflammatory mediators (TNF, IL-6, IL-15, CCL2 and creatine kinase) and the tissue inflammation at day 30 post-infection. Theracurmin therapy reduced the parasitemia curve without altering the animals’ survival rate, and it protected mice from losing body mass. Theracurmin also reduced CCL2 in cardiac tissue, IL-15 in cardiac and skeletal tissue, and plasma CK. Even without effects on TNF and IL-6 production and tissue amastigote nests, Theracurmin reduced the leukocyte infiltrate in both evaluated tissues, even in the case of more effective results observed to the benznidazole treatment. Our data suggest Theracurmin has an immunomodulatory (CCL2, IL-15, CK and tissue leukocyte infiltration) and a trypanocidal effect (on circulating parasites) during experimental infection triggered by the Colombian strain of T. cruzi. Further investigations are necessary to comprehend the Theracurmin role performed in combination with benznidazole or other potential anti-T. cruzi chemical compounds.

The interaction of the anti-beta1-adrenergic receptor autoantibodies (β1ARAb) and the anti-muscarinic M2 receptor autoantibodies (M2RAb) with cardiac neurotransmitter receptors were identified in human chronic Chagas cardiomyopathy (CCC) related to the ECG and dysautonomia disturbances. Dogs are considered gold model to the study of Trypanosoma cruzi infection due the clinical similarities with CCC. This study aims to evaluate whether anti-β1ARAb, anti-β2ARAb, and anti-muscarinic M2RAb are generated in Beagle dogs infected by T. cruzi using Y and Berenice-78 strains of T. cruzi. Animals were infected with 4.0 x 103 bloodstream trypomastigotes/kg of body weight and, after 25 months of infection, blood sample was collected, and serum stored at -80°C. Dog serum was treated by ammonium sulphate precipitation and the IgG antibodies isolated and added to the beating neonatal rats’ cardiomyocytes. All T. cruzi-infected dogs developed agonistic β1ARAb, β2ARAb, and M2RAb. Animals infected by Berenice strain presented less β2ARAb and M2RAb activities than dogs infected by Y strain of the parasite. In cardiomyocytes culture, the antibodies recognized an epitope on the second extracellular loop of the receptors which were similar to findings in human Chagas disease. There was no detection of antibody against G protein-coupled receptor in serum from uninfected dogs. In conclusion, both Y and Berenice-78 strains of T. cruzi induced dog antibodies, whose targets located in the second extracellular loop of the adrenergic and muscarinic receptors were similar to those observed in individuals with CCC. Therefore, our findings highlight dogs as a promisor model to investigate pathogenic roles of functional Ab against G-protein coupled receptors.

IntroductionChagas’ disease is a tropical neglected illness caused by Trypanosoma cruzi and remains one of the most significant causes of morbidity and mortality in South and Central Americas. The disease is caused by a moderate to intense and persistent inflammatory response characterized by local upregulated expression and production of inflammatory mediators that favors the activation and recruitment of distinct cells of the immune system into different tissues to eliminate the parasites. Theracurmin is a curcumin’s derived formulation of nanoparticles. Its anti-inflammatory properties make this bioactive compound a mitigating factor in pathological cases after an overwhelming inflammatory response.MethodsOur research focused on the testicular investigation in 28 mice infected by 103 trypomastigote forms of Colombian strain of T. cruzi and preventively treated with Theracurmin. The mice were treated with 30 mg/Kg of Theracurmin during the period of 30 days. At the 30th day post infection animals were euthanized, and its testicles were collected to morphological and immunological assays.ResultsThe animals infected and treated with Theracurmin presented a reduction in the testicular levels of IL-15 and IL-6. The volume density (%) of the tunica propria was also higher in all infected animals, but Theracurmin decreased this parameter in the treated animals. In the intertubular area, the percentage of some intertubular components was decreased in the infected animals such as the percentage and volume of Leydig cells, connective tissue, and macrophages.DiscussionFurthermore, our data pointed to the daily use of Theracurmin in the diet as a protective element of the testicular function.