title: Interactions between drugs and sulforaphane modulate the drug metabolism enzymatic system.
abstract: BACKGROUND
  Sulforaphane (SFN) is a potent chemopreventive agent, which is widely consumed in diet or as a diet supplement. It modulates the enzymes of II and III metabolism phase. In this paper, the influence of SFN and three commonly consumed drugs: furosemide, verapamil and ketoprofen on II and III metabolisms phase enzymes was studied. We have also investigated if the interactions between SFN and the drugs occur resulting in enzymatic system disturbances.
  
  
  METHODS
  The Caco-2 cells were incubated with SFN and drugs separately or in a mixture simultaneously or subsequently. The impact of the compounds on the cell viability and NADPH:quinine reductase (QR) activity was determined. The expression of glutathione-S-transferase (GST) isoenzymes GSTA3, GSTM1, P-glycoprotein (PgP) and multidrug resistance protein 1 (MRP1) genes was measured by qPCR method. Since these enzymes are regulated by Nrf2 pathway, the localization of Nrf2 (Nuclear erythroid 2-related factor) after exposure to the mixtures of SFN and the drugs was evaluated by confocal microscopy.
  
  
  RESULTS
  SFN was shown to interact antagonistically with the studied drugs. At most cases an increase in enzymatic activity and expression was observed. The most significant changes were observed in case of enzymes regulated by Nrf2: QR, GSTA1 and GSTA3 and also MRP1. PgP was shown to be not altered by the studied compounds. COCNCLUSION: The interaction between SFN and furosemide, verapamil and ketoprofen modify the activity of enzymatic system involved in drug metabolism and transport. This may lead to drug effectiveness alteration and also to multidrug resistance (MDR) development.
authors.affiliation: Confocal Microscopy Laboratory, Department of Cell Biology, National Medicines Institute, Chełmska 30/34, PL 00-725 Warszawa, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Lubelska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Milczarek
authors.forename: Karolina
authors.initials: K
authors.lastname: Modzelewska
authors.forename: Jolanta
authors.initials: J
authors.lastname: Krzysztoń-Russjan
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Fronczyk
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Wiktorska
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004347:Drug Interactions; D005665:Furosemide / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D017879:Isothiocyanates; D007660:Ketoprofen / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*; D014700:Verapamil / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005665:Furosemide; D005982:Glutathione Transferase; D017879:Isothiocyanates; D007660:Ketoprofen; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D016660:NAD(P)H Dehydrogenase (Quinone); D013454:Sulfoxides; D013861:Thiocyanates; D014700:Verapamil; C484555:GSTA1 protein, human; C016766:sulforaphane; C421109:multidrug resistance-associated protein 1