The stepwise selection for ketoconazole resistance induces upregulation of C14-demethylase (CYP51) in Leishmania amazonensis
Mem. Inst. Oswaldo Cruz
;
107(3): 416-419, May 2012. graf
Artigo
em Inglês
| LILACS
| ID: lil-624025
ABSTRACT
Ketoconazole is a clinically safe antifungal agent that also inhibits the growth of Leishmania spp. A study was undertaken to determine whether Leishmania parasites are prone to becoming resistant to ketoconazole by upregulating C14-demethylase after stepwise pharmacological pressure. Leishmania amazonensis promastigotes [inhibitory concentration (IC)50 = 2 µM] were subjected to stepwise selection with ketoconazole and two resistant lines were obtained, La8 (IC50 = 8 µM) and La10 (IC50 = 10 µM). As a result, we found that the resistance level was directly proportional to the C14-demethylase mRNA expression level; we also observed that expression levels were six and 12 times higher in La8 and La10, respectively. This is the first demonstration that L. amazonensis can up-regulate C14-demethylase in response to drug pressure and this report contributes to the understanding of the mechanisms of parasite resistance.
Texto completo:
DisponíveL
Índice:
LILACS (Américas)
Assunto principal:
Leishmania mexicana
/
Regulação para Cima
/
Cetoconazol
/
Antiprotozoários
Idioma:
Inglês
Revista:
Mem. Inst. Oswaldo Cruz
Assunto da revista:
Medicina Tropical
/
Parasitologia
Ano de publicação:
2012
Tipo de documento:
Artigo
País de afiliação:
Brasil
Instituição/País de afiliação:
Instituto Oswaldo Cruz-Fiocruz/BR
/
Universidade Federal do Rio de Janeiro/BR
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