The mitochondrial uncoupler 2,4-dinitrophenol modulates inflammatory and oxidative responses in Trypanosoma cruzi-induced acute myocarditis in mice.

By uncoupling oxidative phosphorylation, 2,4-dinitrophenol (DNP) attenuates reactive oxygen species (ROS) biosynthesis, which are known to aggravate infectious myocarditis in Chagas disease. Thus, the impact of DNP-based chemotherapy on Trypanosoma cruzi-induced acute myocarditis was investigated. C56BL/6 mice uninfected and infected untreated and treated daily with 100 mg/kg benznidazole (Bz, reference drug), 5 and 10 mg/kg DNP by gavage for 11 days after confirmation of T.

Schistosoma mansoni co-infection modulates Chagas disease development but does not impair the effect of benznidazole-based chemotherapy.

The adequate management of parasite co-infections represents a challenge that has not yet been overcome, especially considering that the pathological outcomes and responses to treatment are poorly understood. Thus, this study aimed to evaluate the impact of Schistosoma mansoni infection on the efficacy of benznidazole (BZN)-based chemotherapy in Trypanosoma cruzi co-infected mice. BALB/c mice were maintained uninfected or co-infected with S.

Matrix metalloproteinases inhibition reveals the association between inflammation, collagen accumulation and intestinal translocation of Schistosoma mansoni eggs in vivo.

Schistosomiasis mansoni is a parasitic infection that causes enterohepatic morbidity associated with severe granulomatous inflammation triggered by parasite eggs. In this disease, granulomatous inflammation leads to intestinal erosion and environmental excretion of S. mansoni eggs from feces, an essential process for propagating the parasite and infecting host organisms.

Synthesis and antimicrobial activity of molecular hybrids based on eugenol and chloramphenicol pharmacophores.

In the constant search for new pharmacological compounds, molecular hybridisation is a well-known technique whereby two or more known pharmacophoric subunits are combined to create a new "hybrid" compound. This hybrid is expected to maintain the characteristics of the original compounds whilst demonstrating improvements to their pharmacological action. Accordingly, we report here a series of molecular hybrid compounds based upon eugenol and chloramphenicol pharmacophores.

4-nitrobenzoylcoumarin potentiates the antiparasitic, anti-inflammatory and cardioprotective effects of benznidazole in a murine model of acute Trypanosoma cruzi infection.

The anti-inflammatory and cardioprotective potential of coumarin metabolites in infectious myocarditis remains overlooked. Thus, the impact of the synthetic 4-nitrobenzoylcoumarin (4NB) alone and combined with benznidazole (Bz) in a murine model of Trypanosoma cruzi-induced acute myocarditis was investigated. Swiss mice infected with T.

Impact of diminazene aceturate on renin-angiotensin system, infectious myocarditis and skeletal myositis in mice: An in vitro and in vivo study.

Although renin-angiotensin system (RAS) imbalance is manifested in cardiomyopathies with different etiologies, the impact of RAS effectors on Chagas cardiomyopathy and skeletal myositis is poorly understood. Given that diminazene aceturate (DMZ) shares trypanocidal, angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1-7) stimulatory effects, we investigated the impact of DMZ on cardiomyocytes infection in vitro, renin-angiotensin system, Chagas cardiomyopathy and skeletal myositis in vivo. Cardiomyocytes and T.

Thioridazine aggravates skeletal myositis, systemic and liver inflammation in Trypanosoma cruzi-infected and benznidazole-treated mice.

While thioridazine (Tio) inhibits the antioxidant defenses of Trypanosoma cruzi, the gold standard antitrypanosomal drug benznidazole (Bz) has potent anti-inflammatory and pro-oxidant properties. The combination of these drugs has never been tested to determine the effect on T. cruzi infection.

Could phenothiazine-benznidazole combined chemotherapy be effective in controlling heart parasitism and acute infectious myocarditis?

Phenothiazines inhibit major antioxidant defense mechanisms in trypanosomatids and exhibit potent cytotoxic effects in vitro. However, the relevance of these drugs in the treatment of Trypanosoma cruzi-induced acute myocarditis is poorly explored, especially in combination with reference trypanocidal drugs. Thus, we compared the antiparasitic and cardioprotective potential of thioridazine (TDZ) and benznidazole (Bz) administered in monotherapy and combined in a murine model of T.

Sesquiterpene lactone potentiates the immunomodulatory, antiparasitic and cardioprotective effects on anti-Trypanosoma cruzi specific chemotherapy.

We investigated the immunomodulatory, antiparasitic and cardioprotective effects of a sesquiterpene lactone (SL) administered alone or combined with benznidazole (Bz), in a murine model of Chagas' disease by in vitro and in vivo assays. Antiparasitic and cytotoxic potential of tagitinin C (SL) and Bz were tested in vitro against T. cruzi epimastigotes and cardiomyocytes.

Could angiotensin-modulating drugs be relevant for the treatment of Trypanosoma cruzi infection? A systematic review of preclinical and clinical evidence.

Although leucocytes are targets of renin-angiotensin system (RAS) effector molecules and RAS-modulating drugs exert immunomodulatory effects, their impact on Trypanosoma cruzi infection remains poorly understood. By using the framework of a systematic review, we integrated the preclinical and clinical evidence to investigate the relevance of angiotensin-inhibiting drugs on T. cruzi infections.

Role of cyclooxygenase-2 in Trypanosoma cruzi survival in the early stages of parasite host-cell interaction.

Chagas disease, caused by the intracellular protozoan Trypanosoma cruzi, is a serious health problem in Latin America. During this parasitic infection, the heart is one of the major organs affected. The pathogenesis of tissue remodelling, particularly regarding cardiomyocyte behaviour after parasite infection and the molecular mechanisms that occur immediately following parasite entry into host cells are not yet completely understood.

Myenteric plexus is differentially affected by infection with distinct Trypanosoma cruzi strains in Beagle dogs.

Chagasic megaoesophagus and megacolon are characterised by motor abnormalities related to enteric nervous system lesions and their development seems to be related to geographic distribution of distinct Trypanosoma cruzi subpopulations. Beagle dogs were infected with Y or Berenice-78 (Be-78) T. cruzi strains and necropsied during the acute or chronic phase of experimental disease for post mortem histopathological evaluation of the oesophagus and colon.

Naturally Leishmania infantum-infected dogs display an overall impairment of chemokine and chemokine receptor expression during visceral leishmaniasis.

Dogs are the primary reservoir for Leishmania parasites. The immune response induced by Leishmania infantum infection in these animals has not been completely elucidated, and few studies have investigated the relationship between the expression levels of chemokines and chemokine receptors and the clinical status of dogs with canine visceral leishmaniasis (CVL). The aim of this study was to correlate the clinical status of naturally L.

Increased type 1 chemokine expression in experimental Chagas disease correlates with cardiac pathology in beagle dogs.

Chemokines and chemokine receptors interaction have presented important role in leukocyte migration to specific immune reaction sites. Recently, it has been reported that chemokine receptors CXC (CXCR3) and CC (CCR5) were preferentially expressed on Th1 cells while CCR3 and CCR4 were preferentially expressed on Th2 cells. This study evaluated the mRNA expression of type 1 and type 2 chemokine and chemokine receptors in the cardiac tissue of Beagle dogs infected with distinct genetic groups of Trypanosoma cruzi (Y, Berenice-78 and ABC strains) during acute and chronic phases.

Development of chronic cardiomyopathy in canine Chagas disease correlates with high IFN-gamma, TNF-alpha, and low IL-10 production during the acute infection phase.

When infected with Trypanosoma cruzi, Beagle dogs develop symptoms similar to those of Chagas disease in human beings, and could be an important experimental model for a better understanding of the immunopathogenic mechanisms involved in chronic chagasic infection. This study evaluates IL-10, IFN-gamma and TNF-alpha production in the sera, culture supernatant, heart and cervical lymph nodes and their correlation with cardiomegaly, cardiac inflammation and fibrosis in Beagle dogs infected with T. cruzi.

Trypanosoma cruzi: acute and long-term infection in the vertebrate host can modify the response to benznidazole.

We analyzed the influence of Trypanosoma cruzi maintenance in different hosts (dog and mouse) on its susceptibility to benznidazole treatment. Five T. cruzi stocks were isolated from dogs inoculated with Be-62 or Be-78 strain (both sensitive to benznidazole) 2-10 years ago, and the benznidazole sensitivity was then determined using the mouse as experimental model.