Enhanced liver tumor promotion but not liver initiation activity in rats subjected to combined administration of omeprazole and ß-naphthoflavone.
J Toxicol Sci
; 37(5): 969-85, 2012.
Article
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| MEDLINE
| ID: mdl-23038005
Omeprazole (OPZ) and ß-naphthoflavone (BNF) are cytochrome P450 (CYP)1A inducers and have liver tumor promoting effects. In this study, we investigated the co-promoting and co-initiating effects of OPZ and BNF in rats. In Experiment 1, male rats were subjected to partial hepatectomy (PH), and given oral doses of 138 or 276 mg/kg OPZ, 0.125% or 0.25% BNF or 138 mg/kg OPZ+0.125% BNF (n = 9~12) for 6 weeks after N-diethylnitrosamine (DEN) initiation. In Experiment 2, male rats were treated with oral doses of 138 or 276 mg/kg OPZ, 0.03% or 0.06% BNF or 138 mg/kg OPZ+0.03% BNF (n = 11~12) for 9 days starting 1 week before initiating treatment. As an initiating treatment, 2-Amino-3,4-dimethylimidazo[4,5-f]quinolone (MeIQx) was orally administered 12 hr after PH. The rats were fed a basal diet for 15 days, followed by a diet containing 0.015% 2-acetylaminofluorene for the next 10 days with a single oral dose of carbon tetrachloride. In Experiment 1, the number and area of glutathione S-transferase placental form-positive foci in the OPZ+BNF group were significantly higher than the average values of the High OPZ or the High BNF group. The expression of cyclooxygenase-2 (Cox-2) and COX-2 protein in the liver significantly increased in the OPZ+BNF group. In Experiment 2, liver initiation activity was not enhanced by the co-administration of OPZ+BNF. The results of our studies suggest that the co-administration of OPZ and BNF results in synergistic effects in the liver tumor promotion probably owing to increased COX-2 expression, but no modifying effect in the liver initiation activity of MeIQx in rats.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Omeprazol
/
Carcinógenos
/
Beta-naftoflavona
/
Citocromo P-450 CYP1A1
/
Inhibidores de la Bomba de Protones
/
Neoplasias Hepáticas Experimentales
Límite:
Animals
Idioma:
En
Revista:
J Toxicol Sci
Año:
2012
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Japón