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

Taysa Ribeiro Schalcher, Rosivaldo S. Borges, Michael D. Coleman, João Batista Júnior, Claudio G. Salgado, Jose Luiz F. Vieira, Pedro R.T. Romão, Fabio R. Oliveira, Marta Chagas Monteiro

Research output: Contribution to journalArticle

Abstract

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 MDTsupervised 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.

LanguageEnglish
Article numbere85712
Number of pages9
JournalPLoS ONE
Volume9
Issue number1
DOIs
Publication statusPublished - 22 Jan 2014

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dapsone
leprosy
Dapsone
Oxidative stress
Leprosy
Methemoglobin
Oxidative Stress
oxidative stress
Antioxidants
oxidation
Oxidation
Catalase
therapeutics
Superoxide Dismutase
Nitric Oxide
Clofazimine
Lipids
Plasmas
Molecular modeling
Rifampin

Bibliographical note

Copyright: © 2014 Schalcher et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite this

Ribeiro Schalcher, T., Borges, R. S., Coleman, M. D., Júnior, J. B., Salgado, C. G., Vieira, J. L. F., ... Chagas Monteiro, M. (2014). Clinical oxidative stress during leprosy multidrug therapy: impact of dapsone oxidation. PLoS ONE, 9(1), [e85712]. https://doi.org/10.1371/journal.pone.0085712
Ribeiro Schalcher, Taysa ; Borges, Rosivaldo S. ; Coleman, Michael D. ; Júnior, João Batista ; Salgado, Claudio G. ; Vieira, Jose Luiz F. ; Romão, Pedro R.T. ; Oliveira, Fabio R. ; Chagas Monteiro, Marta. / Clinical oxidative stress during leprosy multidrug therapy : impact of dapsone oxidation. In: PLoS ONE. 2014 ; Vol. 9, No. 1.
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Ribeiro Schalcher, T, Borges, RS, Coleman, MD, Júnior, JB, Salgado, CG, Vieira, JLF, Romão, PRT, Oliveira, FR & Chagas Monteiro, M 2014, 'Clinical oxidative stress during leprosy multidrug therapy: impact of dapsone oxidation' PLoS ONE, vol. 9, no. 1, e85712. https://doi.org/10.1371/journal.pone.0085712

Clinical oxidative stress during leprosy multidrug therapy : impact of dapsone oxidation. / Ribeiro Schalcher, Taysa; Borges, Rosivaldo S.; Coleman, Michael D.; Júnior, João Batista; Salgado, Claudio G.; Vieira, Jose Luiz F.; Romão, Pedro R.T.; Oliveira, Fabio R.; Chagas Monteiro, Marta.

In: PLoS ONE, Vol. 9, No. 1, e85712, 22.01.2014.

Research output: Contribution to journalArticle

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AU - Júnior, João Batista

AU - Salgado, Claudio G.

AU - Vieira, Jose Luiz F.

AU - Romão, Pedro R.T.

AU - Oliveira, Fabio R.

AU - Chagas Monteiro, Marta

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N2 - 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 MDTsupervised 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.

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Ribeiro Schalcher T, Borges RS, Coleman MD, Júnior JB, Salgado CG, Vieira JLF et al. Clinical oxidative stress during leprosy multidrug therapy: impact of dapsone oxidation. PLoS ONE. 2014 Jan 22;9(1). e85712. https://doi.org/10.1371/journal.pone.0085712