Health & Environmental Research Online (HERO)


Print Feedback Export to File
2582084 
Journal Article 
In vitro Interactions with Repeated Grapefruit Juice Administration - to Peel or not to Peel? 
Brill, S; Zimmermann, C; Berger, K; Drewe, J; Gutmann, H 
2009 
1 
Planta Medica
ISSN: 0032-0943
EISSN: 1439-0221 
75 
4 
332-335 
19148864 
WOS:000264895100009 
Interactions of acutely administered grapefruit juice (GFJ) with cytochrome P450 isoform 3A4 (CYP3A4) and P-glycoprotein (Pgp) function are well established. In this study, we investigated in vitro the effect of repeated administration of GFJ and its major constituents (the flavonoid naringin, its aglycone naringenin and the furanocoumarin bergamottin) on mRNA expression of MDR1 and CYP3A4 in LS180 cells. Since the bergamottin content is higher in the peel than in the fruit, we compared GFJ containing peel (GFJP+) with juice without any peel extract (GFJP-). GFJP-(1%) showed no significant effect on MDR1 and CYP3A4 mRNA expression, whereas 1% GFJP+ increased expression of MDR1 3.7-fold (P < 0.01) and CYP3A4 2.3-fold (P < 0.05). Of the tested constituents, only 10 PM bergamottin and 200 mu M naringenin induced MDR1 mRNA levels 2.9- and 4.0-fold, respectively (P < 0.01 for both), and CYP3A4 mRNA levels 3.2- and 15.6-fold (P < 0.01 for both), respectively. Western blot analysis and rhodamine 123 uptake experiments partly confirmed these findings on the protein and the functional level. In summary, GFJ containing no peel extract may have a lower potential for interactions with CYP3A4 or P-glycoprotein. 
grapefruit juice; bergamottin; CYP3A4; P-glycoprotein; Citrus x paradisi Macfad; naringin/naringenin