Modulation of hepatic ABC transporters by Eruca vesicaria intake: Potential diet-drug interactions.
Food Chem Toxicol
; 133: 110797, 2019 Nov.
Article
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| MEDLINE
| ID: mdl-31479713
ABSTRACT
The aim of this work was to evaluate whether oral administration of Eruca vesicaria, a species of rocket cultivated in Argentina, could modify cyclophosphamide (CP)-induced genotoxicity through modulation of hepatic ABC transporters. Daily oral administration of E. vesicaria fresh leaves juice (1.0, 1.4 and 2.0â¯â¯g/kg) for 14 days did not alter genotoxicity biomarkers -alkaline comet assay and micronucleus test -in neither male nor female mice. Instead, repeated intake of this cruciferous decreased CP-induced DNA damage dose-dependently and it caused hepatic overexpression of P-glycoprotein (P-gp; 1.4 and 2.0â¯â¯g/kg) and multidrug resistance protein 2 (MRP2; 2.0â¯â¯g/kg), but not breast cancer resistance protein (Bcrp). The antigenotoxic effect of E. vesicaria was prevented by 50â¯mg/kg verapamil (P-gp inhibitor) or 10â¯mg/kg indomethacin (MRP2 inhibitor). In turn, CP-induced cytotoxicity (10â¯mM, 24â¯h) on human hepatoma cells (HepG2/C3A) was significantly reduced by preincubation with E. vesicaria (1.4â¯mg/ml; 48â¯h); this effect was absent when CP was coincubated with 35⯵M verapamil, 80⯵M indomethacin or 10⯵M KO-143 (BCRP inhibitor). Altogether, these results allow us to demonstrate that repeated intake of E. vesicaria exhibited antigenotoxicity, at least in part, by induction of hepatic ABC transporters in vivo in mice as well as in vitro in human liver cells. This could account for other diet-drug interactions.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Brassica
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Extractos Vegetales
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Mutagénesis
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP
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Sustancias Protectoras
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Subfamilia B de Transportador de Casetes de Unión a ATP
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Food Chem Toxicol
Año:
2019
Tipo del documento:
Article
País de afiliación:
Argentina
Pais de publicación:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
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REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM