In-vitro mutagenic potential and effect on permeability of co-administered drugs across Caco-2 cell monolayers of Rubus idaeus and its fortified fractions.
This study investigated the mutagenic, anti-mutagenic and cytotoxic effects of acetone extract of raspberry, Rubus idaeus L. (v. Ottawa) Rosaceae, and the isolated and characterized ellagitannin and anthocyanin fractions thereof, suitable for food applications. The studied raspberry extract and fractions did not show any mutagenic effects determined in the miniaturized Ames test and were not cytotoxic to Caco-2 cells at the used concentrations. However, the anti-mutagenic properties were changed (i.e. decreased mutagenicity of 2-nitrofluorene in strain TA98, and slightly increased mutagenicity of 2-aminoanthracene in strain TA100) with metabolic activation. Further, their influence on the permeability of co-administered common drugs (ketoprofen, paracetamol, metoprolol and verapamil) across Caco-2 monolayers was evaluated. The apical-to-basolateral permeability of highly permeable verapamil was mostly affected (decreased) during co-administration of the raspberry extract or the ellagitannin fraction. Ketoprofen permeability was decreased by the ellagitannin fraction. Consumption of food rich in phytochemicals, as demonstrated here with chemically characterized raspberry extract and fractions, with well-absorbing drugs would seem to affect the permeability of some of these drugs depending on the components. Thus their effects on the absorption of drugs in-vivo cannot be excluded.
Kreander
Kari
K
Drug Discovery and Development Technology Center, Faculty of Pharmacy, University of Helsinki, Finland.
Galkin
Anna
A
Vuorela
Satu
S
Tammela
Päivi
P
Laitinen
Leena
L
Heinonen
Marina
M
Vuorela
Pia
P
D000082:Acetaminophen / Q000493:pharmacokinetics; D000872:Anthocyanins / Q000302:isolation & purification / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005449:Fluorenes / Q000494:pharmacology; D005638:Fruit / Q000737:chemistry; D006801:Humans; D047348:Hydrolyzable Tannins / Q000302:isolation & purification / Q000494:pharmacology; D007660:Ketoprofen / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D008790:Metoprolol / Q000493:pharmacokinetics; D009152:Mutagenicity Tests / Q000379:methods; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D027824:Rosaceae / Q000737:chemistry*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D014700:Verapamil / Q000493:pharmacokinetics
D000872:Anthocyanins; D005449:Fluorenes; D047348:Hydrolyzable Tannins; D010936:Plant Extracts; C047878:2-nitro-9-fluorenone; D000082:Acetaminophen; D007660:Ketoprofen; D014700:Verapamil; D008790:Metoprolol