Doença de chagas aguda e suas implicacões comportamentais, no perfil oxidativo e sinalização purinérgica em modelo experimental sob terapia com Resveratrol

Abstract

Chagas disease, caused by the flagellate protozoan Trypanosoma cruzi, is endemic to South America and has a wide geographic distribution, but it is still considered a neglected disease. Once installed, Chagas disease causes an intense inflammatory process in the host with activation of immune and inflammatory cascades, with the release of numerous cellular products aimed at controlling parasite multiplication. There are numerous cellular processes involved, and we will highlight here the role of oxidative stress and the purinergic system, through cellular machinery, both processes focused on cellular homeostasis in anti- and pro-inflammatory processes. In addition, we currently have only one pharmacological treatment approved in Brazil. We know that all these cellular processes can be reversed or potentiated by exogenous molecules. In this sense, in this work we studied the effect of the resveratrol molecule (RSV) against an acute infection caused by T. cruzi. For this, we performed three independent experiments to evaluate the function of RSV free or associated with benznidazole (BNZ). In the first study, evaluating RSV against the condition of oxidative stress caused by T. cruzi infection. Our findings suggest that resveratrol did not elicit an adequate antioxidant response, which results in the efficient elimination of reactive oxygen species (ROS) in the liver during acute Chagas disease. No direct or indirect effects of RSV on trypomastigotes were observed; however, RSV stimulated nitrous stress (NOx). In the second study, we evaluated the response of free RSV or in association with BNZ, showing that the association between RVS + BNZ seems to be beneficial with regard to the inflammatory damage caused by the parasitic infection. With regard to effects on purinergic signaling, we observed increases in ATP and ADP hydrolysis by NTPDase in the total cortex of infected animals. RSV treatment in the infected group decreased the hydrolysis of ATP, ADP and AMP compared to the infected group. The combination RSV + BNZ (100mg/kg) decreased AMP hydrolysis in infected animals compared to the INF group, exerting an anti-inflammatory effect. We also evaluated the implication of parasitism and the treatments of free RSV or in association with BNZ in relation to the behavior of mice, at the end of our studies, we can observe that the dose of RSV (100mg/kg for 7 days) used in this study seems to exert beneficial effects, such as the improvement in object recognition in the group treated with RSV+BNZ INF, in addition, data from the literature reveal that in some situations a parasite can adjust the behavioral response of its host to reflect its own interest. In this sense, it may be in the interest of the medical/scientific community to use RSV as an adjuvant in traditional pharmacological therapy for Chagas disease, but further studies are needed to ensure its safe use.