RESUMO

This study aims to assess the oxidative stress in leprosy patients under multidrug therapy (MDT; dapsone, clofazimine and rifampicin), evaluating the nitric oxide (NO) concentration, catalase (CAT) and superoxide dismutase (SOD) activities, glutathione (GSH) levels, total antioxidant capacity, lipid peroxidation, and methemoglobin formation. For this, we analyzed 23 leprosy patients and 20 healthy individuals from the Amazon region, Brazil, aged between 20 and 45 years. Blood sampling enabled the evaluation of leprosy patients prior to starting multidrug therapy (called MDT 0) and until the third month of multidrug therapy (MDT 3). With regard to dapsone (DDS) plasma levels, we showed that there was no statistical difference in drug plasma levels between multibacillary (0.518±0.029 µg/mL) and paucibacillary (0.662±0.123 µg/mL) patients. The methemoglobin levels and numbers of Heinz bodies were significantly enhanced after the third MDT-supervised dose, but this treatment did not significantly change the lipid peroxidation and NO levels in these leprosy patients. In addition, CAT activity was significantly reduced in MDT-treated leprosy patients, while GSH content was increased in these patients. However, SOD and Trolox equivalent antioxidant capacity levels were similar in patients with and without treatment. These data suggest that MDT can reduce the activity of some antioxidant enzyme and influence ROS accumulation, which may induce hematological changes, such as methemoglobinemia in patients with leprosy. We also explored some redox mechanisms associated with DDS and its main oxidative metabolite DDS-NHOH and we explored the possible binding of DDS to the active site of CYP2C19 with the aid of molecular modeling software.

Assuntos

Clofazimina/uso terapêutico , Dapsona/uso terapêutico , Hanseníase/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Rifampina/uso terapêutico , Adulto , Análise de Variância , Catalase/sangue , Citocromo P-450 CYP2C19/metabolismo , Dapsona/sangue , Dapsona/metabolismo , Quimioterapia Combinada , Feminino , Glutationa/sangue , Corpos de Heinz/efeitos dos fármacos , Corpos de Heinz/metabolismo , Humanos , Hansenostáticos/uso terapêutico , Hanseníase/sangue , Masculino , Metemoglobina/metabolismo , Pessoa de Meia-Idade , Oxirredução , Ligação Proteica , Espécies Reativas de Oxigênio/sangue , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem

RESUMO

The mature human erythrocyte, when submitted to oxidative stress, can demonstrate depletion of reduced glutathione, oxidation of the hemoglobin molecule and aggregation of complexes of iron close to the membrane. These can produce abnormalities in the erythrocyte membrane and hemolysis. The aim of this work was to study the antioxidative action of vitamin C (vit. C), deferroxamine (DFO) and the flavonoids quercetin and rutin in normal human erythrocytes, submitted to in vitro oxidative stress induced by tert-butylhydroperoxide ((t)BHP). Venous blood was collected in citrate-phosphate-dextrose (CPD) solution, as anticoagulant, from healthy adult individuals after informed consent. The erythrocytes were resuspended in PBS to obtain 35% globular volume, and then submitted to the oxidative action of (t)BHP for up to 30 min, with or without previous incubation for 60 min with vit. C, DFO, quercetin and rutin. Decrease in the GSH concentration, G6-PD and GR activities, and increase in the methemoglobin and Heinz bodies (HB) formation, occurred with the increase in (t)BHP concentration. (t)BHP did not effect on the membrane proteins detected by SDS-PAGE. Quercetin, partially prevented the GSH decrease and the formation of HB, but did not prevent MetHb formation from oxidative damage by (t)BHP. Rutin, after (t)BHP induction, prevented the GSH decrease and the formation of HB. Vit. C, had no influence on the depletion of GSH, inhibited partially the metHb formation, and it protected GR, but not G6-PD from oxidative damage by (t)BHP. DFO partially inhibited the metHb formation and GSH decrease, but it did not protect GR and G6-PD from oxidative damage by (t)BHP. The results obtained suggest that vit. C, DFO and the flavonoids quercetin and rutin contribute to the decrease in the oxidative stress caused by (t)BHP.

Assuntos

Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Desferroxamina/farmacologia , Eritrócitos/efeitos dos fármacos , Quercetina/farmacologia , Rutina/farmacologia , terc-Butil Hidroperóxido/efeitos adversos , Adulto , Eritrócitos/metabolismo , Feminino , Glucosefosfato Desidrogenase/metabolismo , Glutationa/metabolismo , Corpos de Heinz/efeitos dos fármacos , Corpos de Heinz/metabolismo , Humanos , Masculino , Metemoglobina/metabolismo , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Adulto Jovem

RESUMO

The understanding of the oxidative stress mechanisms helps to explain many of the processes of cellular lesion and death, especially those related to the hemolytic diseases. Sickle cell anemia, thalassemias and G6-PD deficiency are among the more frequent genetic anomalies accompanied by oxidative stress. In the sickle cells, one of the factors that predisposes to the hemolytic process is the oxidative degradation of the hemoglobin S due to its deoxigenation leading to hemichrome formation and precipitation as Heinz bodies. The oxidative stress contributes to the sickle process and shortening of the erythrocyte survival. Here we analyzed the oxidative process in erythrocytes of patients with two different genotypes for HbS (AS and SS). Units of blood from donors of the Center of Hematology and Hemotherapy of Paraná (HEMEPAR), from normal individuals (AA) and from heterozygote individuals (AS), and venous blood collected from patients with sickle cell anemia (SS) were analyzed. In order to evaluate the protective action of the vitamins C and E in oxidative stress, erythrocytes were treated with antioxidant substances, vitamin C and vitamin E, and then treated with the oxidant tert-butilhydroperoxide (TBHP). The oxidative action induced by TBHP was observed in erythrocytes AA

Assuntos

Anemia Falciforme/metabolismo , Eritrócitos/metabolismo , Hemoglobina Falciforme/metabolismo , Estresse Oxidativo , Anemia Falciforme/tratamento farmacológico , Ácido Ascórbico/uso terapêutico , Doadores de Sangue , Eritrócitos/efeitos dos fármacos , Glutationa/sangue , Corpos de Heinz/metabolismo , Hemoglobina Falciforme/efeitos dos fármacos , Humanos , Oxirredução , Valores de Referência , Vitamina E/uso terapêutico

Assuntos

Humanos , Hemólise , Fragilidade Osmótica , Eletroforese , Hemoglobina Fetal/isolamento & purificação , Corpos de Heinz/metabolismo , Hemoglobinas