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Master's Dissertation
DOI
https://doi.org/10.11606/D.60.2005.tde-17052007-163457
Document
Author
Full name
Mauricio Homem de Mello
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2005
Supervisor
Committee
Queiroz, Regina Helena Costa (President)
Machado, Rosangela Gonçalves Peccinini
Santos, Antonio Cardozo dos
Title in Portuguese
N-acetilcisteina e dapsona: avaliação da toxicidade hematológica e bioquímica em ratos Wistar
Keywords in Portuguese
dapsona
metemoglobina
N-acetilcisteína
N-hidroxilamina
Abstract in Portuguese
A dapsona, fármaco de escolha no tratamento da hanseníase, induz hemotoxicidade que está diretamente relacionada à N-hidroxilação sofrida pelo fármaco, uma de suas principais vias de biotransformação, devido à formação de produtos reativos, as N-hidroxilaminas. Com o objetivo de se avaliar a influência da N-acetilcisteína na toxicidade hematológica e bioquímica da dapsona, foi administrado em ratos Wistar, por via intraperitoneal, 40 mg/kg de dapsona em monoterapia e associada à N-acetilcisteína na dose de 75 mg/kg, concomitantemente e previamente. Os resultados obtidos mostraram que a interação entre a N-acetilcisteína e a dapsona potenciava a hemotoxicidade induzida pela dapsona, principalmente pelo incremento da porcentagem de metemoglobinemia. Em relação aos outros parâmetros estudados: glutationa, bilirrubina, lactato desidrogenase, hemograma completo, contagem de reticulócitos, fragilidade osmótica e dosagem de haptoglobina, os resultados encontrados foram controversos e pouco conclusivos. Os dados observados no presente trabalho permitiram evidenciar que a associação da N-acetilcisteína potenciou a hemotoxicidade da dapsona, como comprovado pelas análises estatísticas de variância (ANOVA), através do teste de Tukey-Kramer, com nível de significância fixado em p<0,05.
Title in English
N-acetylcysteine and dapsone: evaluation on hematological and biochemical toxicity in Wistar rats.
Keywords in English
dapsona
metemoglobina
N-acetilcisteína
N-hidroxilamina
Abstract in English
Dapsone is the choice drug to treat leprosy, but induces hemotoxicity. Its damage is directly related to N-hydroxylated metabolites. This is the principal route of metabolism for dapsone, and produces reactive compounds, N-hydroxylamines. To evaluate the influence of N-acetylcysteine on induced hematological and biochemical toxicity by dapsone, it was given to Wistar rats as a monotherapy, at 40 mg/kg or associated to N-acetylcysteine at 75 mg/kg, at the same time or previously. The obtained results shows that the interaction between N-acetylcysteine and dapsone increased the hemotoxicity induced by dapsone, mainly on the methemoglobin percentage increase. Regarding the other studied parameters: glutathione, bilirubin, lactate dehydrogenase (LDH), complete hemogram, reticulocytes counting, osmotic fragility and haptoglobin dosage, results were confusing and lack of conclusions. Data observed in this project allowed to affirm that N-acetylcysteine association improved the dapsone hemotoxicity as showed by statistical variance analysis (ANOVA), by Tukey-Kramer test, with confidence level fixed at p value <0,05.
 
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Publishing Date
2007-05-21
 
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