In-vitro mutagenic potential and effect on permeability of co-administered drugs across Caco-2 cell monolayers of Rubus idaeus and its fortified fractions

Authors

  • Kari Kreander,

    1. Drug Discovery and Development Technology Center, Faculty of Pharmacy, P.O. Box 56, FI-00014 University of Helsinki, Finland.
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  • Anna Galkin,

    1. Drug Discovery and Development Technology Center, Faculty of Pharmacy, P.O. Box 56, FI-00014 University of Helsinki, Finland.
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  • Satu Vuorela,

    1. Division of Food Chemistry, Department of Applied Chemistry and Microbiology, Faculty of Agriculture and Forestry, P.O. Box 27, FI-00014 University of Helsinki, Finland.
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  • Päivi Tammela,

    1. Drug Discovery and Development Technology Center, Faculty of Pharmacy, P.O. Box 56, FI-00014 University of Helsinki, Finland.
    2. Division of Pharmaceutical Biology, Faculty of Pharmacy, P.O. Box 56, FI-00014 University of Helsinki, Finland.
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  • Leena Laitinen,

    1. Drug Discovery and Development Technology Center, Faculty of Pharmacy, P.O. Box 56, FI-00014 University of Helsinki, Finland.
    2. Division of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, P.O. Box 56, FI-00014 University of Helsinki, Finland.
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  • Marina Heinonen,

    1. Division of Food Chemistry, Department of Applied Chemistry and Microbiology, Faculty of Agriculture and Forestry, P.O. Box 27, FI-00014 University of Helsinki, Finland.
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  • Pia Vuorela

    Corresponding author
    1. Drug Discovery and Development Technology Center, Faculty of Pharmacy, P.O. Box 56, FI-00014 University of Helsinki, Finland.
    2. Department of Biochemistry and Pharmacy, Faculty of Mathematics and Natural Sciences, Åbo Akademi University, FI-20520 Turku, Finland.
      Department of Biochemistry and Pharmacy, Faculty of Mathematics and Natural Sciences, Åbo Akademi University, FI-20520 Turku, Finland. E-mail: pia.vuorela@abo.fi
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Department of Biochemistry and Pharmacy, Faculty of Mathematics and Natural Sciences, Åbo Akademi University, FI-20520 Turku, Finland. E-mail: pia.vuorela@abo.fi

Abstract

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.

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