Cafeteria diet-induced obesity remodels immune response in acute Trypanosoma cruzi infection.

BACKGROUND: Obesity is a global problem associated with several conditions, including hypertension, diabetes, arthritis and cardiovascular diseases. With the increase in the prevalence of obesity in recent years, mostly in developing countries, it is important to study its impact on various diseases, including infectious illnesses, such as Chagas disease, caused by the protozoan Trypanosoma cruzi. Considering that a diet rich in salt, sugar, and fat is associated with obesity, this study aimed to evaluate the influence of cafeteria diet (CAF)-induced obesity on immune responses in T. cruzi-infected rats. METHODS: Male Wistar Hannover rats were provided with water and food ad libitum (chow group). The CAF-fed groups received a normal rodent diet or CAF. The animals were intraperitoneally infected with 105 trypomastigote forms of the Y strain of T. cruzi present in the whole blood from a previously infected mouse. RESULTS: CAF-fed rats showed a significant increase in visceral adipose tissue weight compared to chow-fed rats. A significant reduction in CD3+ CD4+ helper splenic T cells was observed in obese-infected rats compared to non-obese-infected rats, as well as CD11b and macrophages. In addition, macrophages from obese animals displayed reduced RT1b levels compared to those from control animals. Moreover, INF-γ, an important factor in macrophage activation, was reduced in obese-infected rats compared with their counterparts. CONCLUSIONS: These results indicate that a CAF can impair the cell-mediated immune response against T. cruzi.

Melatonin decreases circulating Trypanosoma cruzi load with no effect on tissue parasite replication.

Cardiac damage during the acute phase of Chagas disease (CD) is associated with an increase in pro-inflammatory markers and oxidative stress. Melatonin (MEL) has emerged as a promising therapy for CD due to its antioxidant and immunomodulatory properties; however, the protective action of MEL in the cardiac tissue, as well as its direct action on the parasite cycle, is not fully understood. We investigated the effects of MEL on heart parasitism in mice infected with Trypanosoma cruzi and also its effects on the parasitic proliferation in vitro. Our in vivo study showed that MEL reduced circulating parasitemia load, but did not control tissue (heart, liver, and spleen) parasitism in mice. MEL did not prevent the redox imbalance in the left ventricle of infected mice. Our in vitro findings showed that MEL did not inhibit parasites replication within cells, but rather increased their release from cells. MEL did not control parasitism load in the heart or prevent the cardiac redox imbalance induced by acute T. cruzi infection. The hormone controlled the circulating parasitic load, but within cells MEL accelerated parasitic release, a response that can be harmful.

Potent Schistosomicidal Constituents from Garcinia brasiliensis.

Praziquantel is the drug of choice for the treatment of schistosomiasis. However, several strains of Schistosoma mansoni are resistant to praziquantel, making it necessary to discover new drugs that might be used for its treatment. With this in mind, the properties of a schistosomicidal ethanolic extract of Garcinia brasiliensis Mart. epicarp, the fractions obtained by partitioning this extract, including the hexane fractions, ethyl acetate fraction, and the aqueous fraction, and the isolated compounds 7-epiclusianone, a major component from these fractions, and fukugetin were tested in vitro on adult worms of S. mansoni. Mortality, damage to membranes, and excretory system activity were observed at 100.0, 50.0, 75.0, and 14.0 µg/mL for the ethanolic extract of G. brasiliensis Mart. epicarp, its hexane fractions, the ethyl acetate fraction, and 7-epiclusianone, respectively. For 7-epiclusianone, these data were confirmed by fluorescent probe Hoechst 33 258 and resorufin. Additionally, the biocidal effect of 7-epiclusianone was even higher than the hexane fractions. Moreover, an inhibitory effect of 7-epiclusianone on the egg laying of female adult S. mansoni worms was observed in cercariae and schistossomula. Thus, 7-epiclusianone is a promising schistosomicidal compound; however, more studies are needed to elucidate its mechanism of toxicity and to evaluate the in vivo activity of this compound.