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
Article
ي En
| LILACS
| ID: lil-624025
المكتبة المسؤولة:
BR1.1
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.
Key words
النص الكامل:
1
الفهرس:
LILACS
الموضوع الرئيسي:
Leishmania mexicana
/
Up-Regulation
/
Ketoconazole
/
Antiprotozoal Agents
اللغة:
En
مجلة:
Mem. Inst. Oswaldo Cruz
موضوع المجلة:
MEDICINA TROPICAL
/
PARASITOLOGIA
السنة:
2012
نوع:
Article