The aim of the present study was to assess the effects of an anticholinesterase agent, pyridostigmine bromide (Pyrido), on experimental chronic Chagas heart disease in mice. To this end, male C57BL/6J mice noninfected (control:Con) or chronically infected (5 months) with Trypanosoma cruzi (chagasic:Chg) were treated or not (NT) with Pyrido for one month. At the end of this period, electrocardiogram (ECG); cardiac autonomic function; heart histopathology; serum cytokines; and the presence of blood and tissue parasites by means of immunohistochemistry and PCR were assessed. In NT-Chg mice, significant changes in the electrocardiographic, autonomic, and cardiac histopathological profiles were observed confirming a chronic inflammatory response. Treatment with Pyrido in Chagasic mice caused a significant reduction of myocardial inflammatory infiltration, fibrosis, and hypertrophy, which was accompanied by a decrease in serum levels of IFNγ with no change in IL-10 levels, suggesting a shift of immune response toward an anti-inflammatory profile. Lower nondifferent numbers of parasite DNA copies were observed in both treated and nontreated chagasic mice. In conclusion, our findings confirm the marked neuroimmunomodulatory role played by the parasympathetic autonomic nervous system in the evolution of the inflammatory-immune response to T. cruzi during experimental chronic Chagas heart disease in mice.
Spirulina platensis (SPI) is a microalga with a high content of functional compounds, such as phenolics, phycocyanins and polysaccharides that has been shown to have antioxidant, anti-inflammatory, hypoglycemic, neuroprotective and immunomodulatory effects. The objectives of the present work were to study the possible effects of SPI treatment on the glycemic-lipid profile, oxidative stress, lipid peroxidation and cardiac performance in diabetic rats. Diabetes was induced by streptozotocin (STZ) in male Wistar rats. In diabetic animals SPI, at a dose of 50 mg/kg/day, reduced lipid peroxidation, nitrite levels and lipids in plasma and tissues. SPI exhibited an effective improvement on +dP/dT and −dP/dT in non-diabetic rats. This study showed that SPI significantly suppressed nitrite generation and lipoperoxidation in the hearts of diabetic animals, as well as an improvement in the cardiac function in control SPI-treated rats which is consistent with several studies that demonstrated the protective effect of antioxidants on oxidative stress-mediated injury caused by reactive oxygen species (ROS) produced in diabetic myocardial tissues.
Trypanosoma cruzi is an intracellular parasite that causes Chagas disease that affects millions of people worldwide. Many cellular and molecular aspects of this neglected disease are not fully understood. Prior studies have shown that galectin-1 (Gal-1), a β-galactoside-binding protein that regulates leukocyte recruitment to the inflammatory site, and promotes T. cruzi infection, but the mechanism is unclear. Here, we report that C57BL/6 mice lacking Gal-1 (Lgals1-/-) exhibited lower parasitemia and higher survival rates than their wildtype (WT) counterparts when infected with T. cruzi Y strain. Two weeks after infection, Lgals1-/- mice displayed greater neutrophil accumulation in infection site and heart tissue than WT mice. In T. cruzi-infected Lgals1-/- mice, infiltrated neutrophils produced increased levels of reactive oxygen species (ROS), while macrophages and neutrophils produced increased levels of nitric oxide (NO), which reduced replication and viability of parasites in vitro and downregulated IL-1β production. Pharmacological inhibition of NADPH oxidase and NO synthase during early in vivo infection reversed the protective effect of Gal-1 deficiency in Lgals1-/- mice. Together, our findings demonstrate that lacking Gal-1 favors neutrophil migration to the infection site and increases production of ROS and NO, thereby controlling the early steps of T. cruzi infection by reducing parasitemia and prolonging survival of infected mice.
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