Effects of rivastigmine on the pathogenesis of the experimental trypanosomiasis

Inflammation is important mechanism in Chagas disease (CD) pathogenesis. Considering that CD treatment presents a limited efficacy and anticholinesterase drugs may have antiinflamamtory properties, they could be used as a therapeutic option. We decided evaluate the action of rivastigmine on the anti-inflammatory cholinergic pathway during the course of CD. For this, 120 "Swiss" mice were divided into three groups: 30, 60 and 180 days, and subdivided into four subgroups: Uninfected/untreated (CTRL); uninfected/treated with rivastigmine (RIV); infected/treated (INF + RIV) and infected/untreated (INF). The INF + RIV and INF groups were intraperitoneally inoculated with 5 × 10⁴ trypomastigote forms of Trypanosoma cruzi QM2 strain. Parasitemia, histopathological, GSH, FRAP, TBARS tissue, BChE, AChE and in silico analysis were determined. We observed a decrease in parasitemia and mortality in the animals of the INF + RIV group. The increase in GSH in the INF + RIV and INF groups indicated oxidative damage in the acute phase, nevertheless no significant difference was observed in FRAP, tissue and histopathological TBARS between the infected and control groups. An increase in BChE activity was observed in the INF + RIV and INF groups in all periods studied, yet, the AChE activity was lower in the INF and INF + RIV groups only at 60 days post-infection. In silico analysis revealed that AChE exerts a catalytic role on ACh through the catalytic triad (Ser²⁰⁰; HIS⁴⁴⁰; Glu³²⁷), rivastigmine being associated with the His⁴⁴⁰ binding site. Rivastigmine reduced parasitemia and mortality in vivo in the acute phase of infection, suggesting a potential modulatory role on the non-neuronal cholinergic pathway, although further studies are required to understand it.