Cytochrome P450 1A1/2 induction by antiparasitic drugs: dose-dependent increase in ethoxyresorufin O-deethylase activity and mRNA caused by quinine, primaquine and albendazole in HepG2 cells.
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Bapiro TE, Andersson TB, Otter C, Hasler JA, Masimirembwa CM
Cytochrome P450 1A1/2 induction by antiparasitic drugs: dose-dependent increase in ethoxyresorufin O-deethylase activity and mRNA caused by quinine, primaquine and albendazole in HepG2 cells.
Eur J Clin Pharmacol. 2002 Nov;58(8):537-42. Epub 2002 Oct 2.
- PubMed ID
- 12451431 [ View in PubMed]
- Abstract
OBJECTIVE: To investigate the inductive effects of twenty-four antiparasitic drugs on cytochrome P450 (CYP) 1A1 and 1A2 enzyme activities. METHODS: Human hepatoma (HepG2) cells were exposed to antiparasitic drugs for 24 h, and the ethoxyresorufin O-deethylase (EROD) activity, indicative of CYP1A enzyme activity, was measured fluorometrically. In addition, the CYP1A1 and CYP1A2 mRNA expression levels were determined by means of quantitative reverse-transcriptase polymerase chain reaction. RESULTS: Quinine, albendazole and primaquine caused a dose-dependent increase in EROD activity of 5.5, 4.0 and 7.5-fold, at concentrations eliciting maximal induction, respectively. 2,3,7,8-tetrachlorodibenzo- p-dioxin, used as a positive control at a final concentration of 1.5 nM, caused a 30-fold increase in EROD activity. The induction of EROD activity was accompanied by an increase in CYP1A1 and CYP1A2 mRNA expression levels. Niclosamide, 4-chlorophenylbiguanide, dapsone, amodiaquine and desethylamodiaquine caused slight increases in EROD activity. No effect on CYP1A was observed for artemisinin, suramin, diethylcarbamazine, pyrimethamine, metrifonate, ivermectin, pyrantel artesunate, cycloguanil, atovaquone, melarsoprol, praziquantel, proguanil and dihydroartemisinin. CONCLUSIONS: Quinine, albendazole and primaquine induce CYP1A1 and CYP1A2 at the transcriptional level. Considering the plasma concentrations (C(max)) achieved in vivo after administration of a therapeutic dose, induction by quinine and albendazole might be of clinical significance. The induction by primaquine, however, may not be of pharmacological or toxicological significance as concentrations at which it occurs are much higher than those attained in vivo.
DrugBank Data that Cites this Article
- Drugs
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Albendazole Cytochrome P450 1A1 Protein Humans UnknownInducerDetails Albendazole Cytochrome P450 1A2 Protein Humans UnknownInducerDetails Primaquine Cytochrome P450 1A1 Protein Humans UnknownInducerDetails Primaquine Cytochrome P450 1A2 Protein Humans UnknownSubstrateInducerDetails Quinine Cytochrome P450 1A1 Protein Humans UnknownInhibitorInducerDetails - Pharmaco-transcriptomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Albendazole Approved Vet Approved CYP1A1 1543 upregulated Albendazole results in increased expression of CYP1A1 mRNA 15q24.1 Albendazole Approved Vet Approved CYP1A2 1544 upregulated Albendazole results in increased expression of CYP1A2 mRNA 15q24.1 Primaquine Approved CYP1A1 1543 upregulated Primaquine results in increased expression of CYP1A1 mRNA 15q24.1 Primaquine Approved CYP1A2 1544 upregulated Primaquine results in increased expression of CYP1A2 mRNA 15q24.1 Quinine Approved CYP1A1 1543 upregulated Quinine results in increased expression of CYP1A1 mRNA 15q24.1 Quinine Approved CYP1A2 1544 upregulated Quinine results in increased expression of CYP1A2 mRNA 15q24.1