Modulation of hepatic ABC transporters by Eruca vesicaria intake: Potential diet-drug interactions

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 2.0  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 2.0  g/kg) and multidrug resistance protein 2 (MRP2; 2.0  g/kg), but not breast cancer resistance protein (Bcrp). The antigenotoxic effect of E. vesicaria was prevented by 50 mg/kg verapamil (P-gp inhibitor) or 10 mg/kg indomethacin (MRP2 inhibitor). In turn, CP-induced cytotoxicity (10 mM, 24 h) on human hepatoma cells (HepG2/C3A) was significantly reduced by preincubation with E. vesicaria (1.4 mg/ml; 48 h); this effect was absent when CP was coincubated with 35 μM verapamil, 80 μM indomethacin or 10 μM KO-143 (BCRP inhibitor).