ABSTRACT
Trypanosoma cruzi strains from distinct geographic areas show differences in drug resistance and association between parasites genetic and treatment response has been observed. Considering that benznidazole (BZ) can reduce the parasite burden and tissues damage, even in not cured animals and individuals, the goal is to assess the drug response to BZ of T. cruzi II strains isolated from children of the Jequitinhonha Valley, state of Minas Gerais, Brazil, before treatment. Mice infected and treated with BZ in both phases of infection were compared with the untreated and evaluated by fresh blood examination, haemoculture, polymerase chain reaction, conventional (ELISA) and non-conventional (FC-ALTA) serologies. In mice treated in the acute phase, a significant decrease in parasitaemia was observed for all strains. Positive parasitological and/or serological tests in animals treated during the acute and chronic (95.1-100%) phases showed that most of the strains were BZ resistant. However, beneficial effect was demonstrated because significant reduction (p < 0.05%) and/or suppression of parasitaemia was observed in mice infected with all strains (acute phase), associated to reduction/elimination of inflammation and fibrosis for two/eight strains. BZ offered some benefit, even in not cured animals, what suggest that BZ use may be recommended at least for recent chronic infection of the studied region.
Subject(s)
Humans , Drug Discovery , Industrial Waste/analysis , Nootropic Agents/isolation & purification , Plant Extracts/chemistry , Plant Shoots/chemistry , Stilbenes/isolation & purification , Vitis/chemistry , Agriculture/economics , Amyloid beta-Peptides/antagonists & inhibitors , Amyloid beta-Peptides/metabolism , Benzofurans/analysis , Benzofurans/chemistry , Benzofurans/economics , Benzofurans/isolation & purification , Chromatography, High Pressure Liquid , France , Industrial Waste/economics , Molecular Structure , Neuroprotective Agents/chemistry , Neuroprotective Agents/economics , Neuroprotective Agents/isolation & purification , Neuroprotective Agents/pharmacology , Nootropic Agents/chemistry , Nootropic Agents/economics , Nootropic Agents/pharmacology , Protein Aggregation, Pathological , Peptide Fragments/antagonists & inhibitors , Peptide Fragments/metabolism , Phenols/chemistry , Phenols/economics , Plant Extracts/economics , Protein Aggregates/drug effects , Spectrometry, Mass, Electrospray Ionization , Stereoisomerism , Stilbenes/analysis , Stilbenes/chemistry , Stilbenes/economics , Stilbenes/pharmacologyABSTRACT
Angiotensin-(1-7) (Ang-(1-7)) is now considered to be a biologically active member of the renin-angiotensin system. The functions of Ang-(1-7) are often opposite to those attributed to the main effector component of the renin-angiotensin system, Ang II. Chronic administration of angiotensin-converting enzyme inhibitors (ACEI) increases 10- to 25-fold the plasma levels of this peptide, suggesting that part of the beneficial effects of ACEI could be mediated by Ang-(1-7). Ang-(1-7) can be formed from Ang II or directly from Ang I. Other enzymatic pathways for Ang-(1-7) generation have been recently described involving the novel ACE homologue ACE2. This enzyme can form Ang-(1-7) from Ang II or less efficiently by the hydrolysis of Ang I to Ang-(1-9) with subsequent Ang-(1-7) formation. The biological relevance of Ang-(1-7) has been recently reinforced by the identification of its receptor, the G-protein-coupled receptor Mas. Heart and blood vessels are important targets for the formation and actions of Ang-(1-7). In this review we will discuss recent findings concerning the biological role of Ang-(1-7) in the heart and blood vessels, taking into account aspects related to its formation and effects on these tissues. In addition, we will discuss the potential of Ang-(1-7) and its receptor as a target for the development of new cardiovascular drugs.