RESUMO
Dapsone (DDS) hydroxylamine metabolites cause oxidative stress- linked adverse effects in patients, such as methemoglobin formation and DNA damage. This study evaluated the ameliorating effect of the antioxidant resveratrol (RSV) on DDS hydroxylamine (DDS-NHOH) mediated toxicity in vitro using human erythrocytes and lymphocytes. The antioxidant mechanism was also studied using in-silico methods. In addition, RSV provided intracellular protection by inhibiting DNA damage in human lymphocytes induced by DDS-NHOH. However, whilst pretreatment with RSV (10-1000 µM significantly attenuated DDS-NHOH-induced methemoglobinemia, but it was not only significantly less effective than methylene blue (MET), but also post-treatment with RSV did not reverse methemoglobin formation, contrarily to that observed with MET. DDS-NHOH inhibited catalase (CAT) activity and reactive oxygen species (ROS) generation, but did not alter superoxide dismutase (SOD) activity in erythrocytes. Pretreatment with RSV did not alter these antioxidant enzymes activities in erythrocytes treated with DDS-NHOH. Theoretical calculations using density functional theory methods showed that DDS-NHOH has a pro-oxidant effect, whereas RSV and MET have antioxidant effect on ROS. The effect on methemoglobinemia reversion for MET was significantly higher than that of RSV. These data suggest that the pretreatment with resveratrol may decrease heme-iron oxidation and DNA damage through reduction of ROS generated in cells during DDS therapy.
Assuntos
Antioxidantes/farmacologia , Dapsona/análogos & derivados , Substâncias Protetoras/farmacologia , Estilbenos/farmacologia , Adulto , Catalase/metabolismo , Células Cultivadas , Dapsona/farmacologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Feminino , Humanos , Masculino , Metemoglobina/metabolismo , Metemoglobinemia/tratamento farmacológico , Metemoglobinemia/metabolismo , Pessoa de Meia-Idade , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Resveratrol , Superóxido Dismutase/metabolismo , Adulto JovemRESUMO
The genus Panstrongylus includes 14 species widely distributed from Mexico to Argentina, some of them with great epidemiological significance as vectors of Chagas disease. We study the karyotype and the male meiotic process of Panstrongylus chinai, P. geniculatus, P. herreri, P. lignarius, P. megistus, P. rufotuberculatus and P. tupynambai. All species present the same sex mechanism (X(1)X(2)Y in males and X(1)X(1)X(2)X(2) in females) and they also have 20 autosomes, with the exception of P. megistus that only presents 18 autosomes. The analysis of C-banding patterns and meiotic chromosome behaviour show a great level of variability allowing the identification of three clearly differentiated groups. In the first group, we only include P. megistus because of its unusual number of autosomes. The second group includes P. chinai, P. herreri, P. lignarius and P. rufotuberculatus. Their autosomes present terminal heterochromatic regions that appear scattered throughout the nucleus and associated with the sex chromosomes. Actually, P. herreri and P. lignarius can be considered cytogenetically identical. Our results are in agreement with morphological, ecological and molecular data indicating that they should be regarded as the same species. The third group only includes P. tupynambai that shows autosomes without C-positive regions. Panstrongylus geniculatus shares characters will all the three groups. Its karyotypic features are extremely polymorphic depending on their geographic origin. Some populations do not show any heterochromatic regions, while others exhibit few or several heterochromatic blocks. The chromosomal variability observed, together with its wide distribution and phenetic variability, suggest that P. geniculatus is a species complex comprising at least two distinct species. Considering the entire subfamily, the level of cytogenetic variation in Panstrongylus is lower than that observed in Triatoma but considerably more than that of Rhodnius, which is a very homogenous genus in terms of chromosome appearance and behaviour. This would endorse the closer relationship between Panstrongylus and Triatoma, and their divergence from Rhodnius, in accordance with current tribal classification.
Assuntos
Doença de Chagas/transmissão , Cromossomos/genética , Evolução Molecular , Insetos Vetores/genética , Panstrongylus/genética , Animais , Citogenética , Feminino , Cariotipagem , Masculino , América do SulRESUMO
Os autores apresentam os resultados do estudo epidemiológico de um caso autóctone da fase aguda da doença de Chagas na ilha do Mosqueiro. Estado do Pará, aproximadamente 75km da capital, Belém. O caso já havia sido objeto de uma publicaçäo anterior. Agora säo apresentadas informaçöes epidemiológicas. Nas proximidades da casa do paciente foram capturados em duas palmeiras de Inajá (Maximilian regia) e em uma da Mucajá (Acrocomia sclerocarpia) 114 triatomineos: Rhodnius pictipes, R. robustus, Panstrongylus lignarius, P. geniculatus e Microtriatoma trinidadensis, com tripanossomas em 31 deles. Na casa do paciente foram encontrados exemplares de Rhodnius pictipes, infectados com formas metacíclicas do Trypanosoma cruzi. Em 14 marsupiais, capturados na localidade, haviam 3 infectados com organismos semelhantes ao T. cruzi. A eletroforese dos isoenzimas nos tripanossomas isolados do paciente, de R. pictipes e de Didelphis marsupialis os classificou como zimodema 1. Os autores concluem que a doença de Chagas do paciente teve origem silvestre
