Alpha-Lipoic Acid and Its Enantiomers Prevent Methemoglobin Formation and DNA Damage Induced by Dapsone Hydroxylamine: Molecular Mechanism and Antioxidant Action.

Dapsone (DDS) therapy can frequently lead to hematological side effects, such as methemoglobinemia and DNA damage. In this study, we aim to evaluate the protective effect of racemic alpha lipoic acid (ALA) and its enantiomers on methemoglobin induction. The pre- and post-treatment of erythrocytes with ALA, ALA isomers, or MB (methylene blue), and treatment with DDS-NOH (apsone hydroxylamine) was performed to assess the protective and inhibiting effect on methemoglobin (MetHb) formation. Methemoglobin percentage and DNA damage caused by dapsone and its metabolites were also determined by the comet assay. We also evaluated oxidative parameters such as SOD, GSH, TEAC (Trolox equivalent antioxidant capacity) and MDA (malondialdehyde). In pretreatment, ALA showed the best protector effect in 2.5 µg/mL of DDS-NOH. ALA (1000 µM) was able to inhibit the induced MetHb formation even at the highest concentrations of DDS-NOH. All ALA tested concentrations (100 and 1000 µM) were able to inhibit ROS and CAT activity, and induced increases in GSH production. ALA also showed an effect on DNA damage induced by DDS-NOH (2.5 µg/mL). Both isomers were able to inhibit MetHb formation and the S-ALA was able to elevate GSH levels by stimulating the production of this antioxidant. In post-treatment with the R-ALA, this enantiomer inhibited MetHb formation and increased GSH levels. The pretreatment with R-ALA or S-ALA prevented the increase in SOD and decrease in TEAC, while R-ALA decreased the levels of MDA; and this pretreatment with R-ALA or S-ALA showed the effect of ALA enantiomers on DNA damage. These data show that ALA can be used in future therapies in patients who use dapsone chronically, including leprosy patients.

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. .

[Detection of new cases of leprosy in the City of Prudentópolis, PR: the analysis from 1998 to 2005]. / Detecção de casos novos de hanseníase no município de Prudentópolis, PR: uma análise de 1998 a 2005.

The aim of this study was to evaluate the detection of new cases of leprosy in Prudentópolis, State of Paraná, from 1998 to 2005. Additionally, we investigated the age group and predominant clinical form of leprosy cases. Data were obtained from clinical-epidemiological records of confirmed leprosy cases that were notified in the Information System for Notifiable Diseases, between 1998 and 2005. Over this period, 222 leprosy cases were notified, of which 63% presented the multibacillary form, with predominance of the Virchow clinical form, thus indicating a process of intense disease transmission. Among these leprosy cases, 35% of the patients were at an economically active age (31 to 45 years old). These indicators showed that there was a high level of bacillus circulation in the community, considering that one risk factor for infection by the bacillus Mycobacterium leprae is contact with untreated individuals who have the multibacillary form. This is despite the drastic reduction in leprosy prevalence over the last two decades, through the implementation of polychemotherapy and other preventive measures.

Detecção de casos novos de hanseníase no município de Prudentópolis, PR: uma análise de 1998 a 2005 / Detection of new cases of leprosy in the City of Prudentópolis, PR: the analysis from 1998 to 2005

Este trabalho teve como objetivo detectar os casos novos de hanseníase do período de 1998 a 2005 no município de Prudentópolis, PR. Assim como, verificar a faixa etária e a forma clínica predominante entre os casos de hanseníase. Os dados foram obtidos através das fichas clínico-epidemiológicas de casos com diagnóstico definitivo de hanseníase notificado no Sistema de Informação sobre Agravos de Notificação, de 1998 a 2005. Neste período, foram relatados 222 casos de hanseníase, dos quais 63 por cento apresentavam a forma multibacilar, com predominância da forma clínica virchowiana, indicando um processo de intensa transmissão da doença. Dos casos de hanseníase, 35 por cento dos pacientes se encontravam na faixa economicamente ativa, 31 a 45 anos. Esses indicadores apontam para uma elevada circulação do bacilo na comunidade, já que um fator de risco para infecção pelo bacilo Mycobacterium Leprae é o contato com pacientes com a forma multibacilar, sem tratamento, embora nas duas últimas décadas, tenha havido redução drástica da prevalência da hanseníase pela implementação da poliquimioterapia e outras medidas preventivas.

The aim of this study was to evaluate the detection of new cases of leprosy in Prudentópolis, State of Paraná, from 1998 to 2005. Additionally, we investigated the age group and predominant clinical form of leprosy cases. Data were obtained from clinical-epidemiological records of confirmed leprosy cases that were notified in the Information System for Notifiable Diseases, between 1998 and 2005. Over this period, 222 leprosy cases were notified, of which 63 percent presented the multibacillary form, with predominance of the Virchow clinical form, thus indicating a process of intense disease transmission. Among these leprosy cases, 35 percent of the patients were at an economically active age (31 to 45 years old). These indicators showed that there was a high level of bacillus circulation in the community, considering that one risk factor for infection by the bacillus Mycobacterium leprae is contact with untreated individuals who have the multibacillary form. This is despite the drastic reduction in leprosy prevalence over the last two decades, through the implementation of polychemotherapy and other preventive measures.