Clinical oxidative stress during leprosy multidrug therapy: impact of dapsone oxidation.

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.

Antioxidant factors, nitric oxide levels, and cellular damage in leprosy patients.

INTRODUCTION: The immune response caused by Mycobacterium leprae is a risk factor for the development of oxidative stress (OS) in leprosy patients. This study aimed to assess OS in leprosy patients before the use of a multidrug therapy. METHODS: We evaluated the nitric oxide (NO) concentration; antioxidant capacity; levels of malondialdehyde, methemoglobin and reduced glutathione; and the activity of catalase and superoxide dismutase (SOD) in leprosy patients. RESULTS: We observed lower SOD activity in these leprosy patients; however, the NO levels and antioxidant capacity were increased. CONCLUSIONS: The infectious process in response to M. leprae could primarily be responsible for the OS observed in these patients.

Antioxidant factors, nitric oxide levels, and cellular damage in leprosy patients

Introduction The immune response caused by Mycobacterium leprae is a risk factor for the development of oxidative stress (OS) in leprosy patients. This study aimed to assess OS in leprosy patients before the use of a multidrug therapy. Methods We evaluated the nitric oxide (NO) concentration; antioxidant capacity; levels of malondialdehyde, methemoglobin and reduced glutathione; and the activity of catalase and superoxide dismutase (SOD) in leprosy patients. Results We observed lower SOD activity in these leprosy patients; however, the NO levels and antioxidant capacity were increased. Conclusions The infectious process in response to M. leprae could primarily be responsible for the OS observed in these patients. .

Quimioterapia da malária causada por plasmodium falciparum / Chemotherapy of malaria caused by plasmodium falciparum

Objetivo: compreender como os antimaláricos utilizados contra o Plasmodium falciparum vêmatuando no decorrer do tempo enfatizando os casos de resistência. Método: feita uma revisão daquimioterapia utilizada contra essa espécie de plasmódio, relatando diversas pesquisas voltadas aresistência aos antigos tratamentos utilizados e o surgimento de novos esquemas terapêuticos.Considerações finais: Arteméter-Lumefantrina foi adotado como primeira linha de tratamento paramalária na África, levando o Ministério da Saúde do Brasil, em 2006, a implantar esta combinaçãonos estados da Amazônia legal que apresentam casos de malária falciparum resistente a terapiapadrão.

Objective: understand how antimalarials used against Plasmodium falciparum has been in thecourse of time emphasizing the cases of resistance. Method: a review of chemotherapy usedagainst this species of plasmodium, reporting several studies focused on resistance to oldertreatments and the emergence of new therapeutic regimens. Final Thoughts:Arteméter+Lumefantrine was adopted as first line treatment for malaria in Africa, prompting theMinistry of Health of Brazil, in 2006, to deploy this combination in the legal Amazonpresenting cases of falciparum malaria resistant to standard therapy.