Induction of cytochrome P450 enzymes by albendazole treatment in the rat.
The anthelmintic drug albendazole (ABZ), methyl(5-(propylthio)-1H-benzimidazol-2-yl)carbamate, is a benzimidazole highly efficient in the treatment of neurocysticercosis. The effects of ABZ treatment (i.p. and p.o. administration) on the expression of several cytochrome P450 (CYP) enzymes were evaluated in rat liver in order to characterize the spectrum of altered CYP enzymes involved in the metabolism of environmental mutagens and carcinogens, after drug intake. Intraperitoneal administration of ABZ (50 mg/kg body weight/day/three days in corn oil) to rats, caused an induction of hepatic activities of CYP1A1-associated ethoxyresorufin O-deethylase (EROD) 65 fold, CYP1A2-associated methoxyresorufin O-demethylase (MROD) 6 fold, CYP2B1-associated penthoxyresorufin O-dealkylase (PROD) 4 fold, CYP2B2-associated benzyloxyresorufin O-dealkylase (BROD) 14 fold, as well as a partial reduction of CYP2E1-associated 4-nitrophenol hydroxylase (4-NPH) activity. CYP3A-associated erythromycin N-demethylase (END) activity was not modified under the same treatment conditions. Western blot analysis was conducted to explore if the increased catalytic activity was a result of an increased protein content; only CYP1A1/2 showed a visible increase in protein concentration after ABZ inoculation, therefore, the increased PROD and BROD activities could be attributed to the induction of CYP1A1/2. Results with the two main metabolites of ABZ (15 mg/kg body weight/day/three days, i.p.) indicated that ABZ sulfoxide (ABZSO) but not ABZ sulfone (ABZSO(2)) displayed the same pattern of CYP induction than ABZ. Oral administration of ABZ at the human therapeutic dose of 20 mg/kg body weight/day/three days, produced an increase in CYP1A1/2 protein content 24 h after the first intake. The protein level remained high during the treatment, and up to 72 h after the last administration; basal protein levels were almost recovered 48 h later.
Asteinza
J
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70228, Ciudad Universitaria, DF 04510, México, Mexico
Camacho-Carranza
R
Reyes-Reyes
RE
Dorado-González
V
Espinosa-Aguirre
JJ