In vitro protective effect and antioxidant mechanism of Resveratrol induced by Dapsone Hydroxylamine in human cells

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 (DDSNHOH) 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

2 nd Brazilian Consensus on Chagas Disease, 2015

Abstract Chagas disease is a neglected chronic condition with a high burden of morbidity and mortality. It has considerable psychological, social, and economic impacts. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on the articulation and strategic contribution of renowned Brazilian experts with knowledge and experience on various aspects of the disease. It is the result of a close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. It is hoped that this document will strengthen the development of integrated actions against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research

Epidemiologia de um caso de doença de Chagas na Ilha do Mosqueiro - Pará

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. 0 caso já havia sido objeto de uma publicação anterior. Agora são apresentadas informações epidemiológicas. Nas proximidades da casa do paciente foram capturados em duas palmeiras de Inajá ('Maximilian regi ay e em uma de Mucajá (Acrocomia sclerocarpia) 114 triatomíneos: 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.<br>The authors present the results of an epidemiological study relating to a case of acute Chagas' disease acquired in the island of Mosqueiro, State of Para, approximately 75 km from the capital Belem. The patient has been the object of a previous publication but now epidemiological information is reported. Near the house of the patient in two Inaja palm trees (Maximilian regia) and one Mucaja palm (Acrocomia sclerocarpia) 114 triatomine bugs were captured of the following species: Rhodnius pictipes, R. robustus, Panstrongylus lignarius, P. geniculatus and Microtriatoma trinidadensis. Trypanosomes were found in 31 bugs. In the house of the patient specimens of R. pictipes were captured infected with metacyclic forms óf Trypanosoma cruzi. In 14 marsupials captured in the locality three had infections with cruzi like trypanosomes. Enzyme electrophoresis of the trypanosomes isolated from the patient, R. pictipes and Didelphis marsupialis were classified as zymodeme 1. The authors conclude that the patients Chagas' disease was of sylvatic origin

In Vitro Protective Effect and Antioxidant Mechanism of Resveratrol Induced by Dapsone Hydroxylamine in Human Cells.

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

Redox mechanism.

<p>Ionization potential and stabilization energy of dapsone hydroxylamine (DDS-NHOH), resveratrol (RSV), and methylene blue (MET) on antioxidant and methemoglobinemia reversion.</p

CAT and SOD activity.

<p>Erythrocytes were pretreated with resveratrol (RSV, 100 μM and 1000 μM) for 1 h at 37°C and incubated for 30 min with DDS-NHOH (2.5 μg/ml) or T-BHP (200 μM). Results are expressed as mean ± S.E.M. *P < 0.05 compared to methanol group.</p

Proposal for a possible action mechanism of resveratrol (RSV) in inhibiting methemoglobin formation and DNA damage induced by DDS hydroxylamine (DDS-NHOH) <i>in vitro</i> model.

<p>Proposal for a possible action mechanism of resveratrol (RSV) in inhibiting methemoglobin formation and DNA damage induced by DDS hydroxylamine (DDS-NHOH) <i>in vitro</i> model.</p

Comparative effect of post-treatment with resveratrol (RSV) or methylene blue (MET) on methemoglobin formation induced by DDS-NHOH.

<p>Erythrocytes were incubated for 1 h with DDS-NHOH (2.5 μg/mL), then these cells were incubated with RSV (100μM) for 1 h or MET(40 nM). Data are reported as mean ± S.E.M. *P < 0.05 compared to methanol group. ^#P < 0.05 compared to DDS-NHOH group.</p