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Sulforaphane - a modulator of detoxifying enzymes can alter medicines effectiveness.

Katarzyna Wiktorska ,  Katarzyna Lubelska ,  Małgorzata Milczarek 

National Medicines Institute (NIL), Chełmska 30/34, Warszawa 00-725, Poland

Abstract

Sulforaphane (SFN) belongs to the group of isothiocyanates which occurs naturally in vegetables from Brassica family.  Due to its chemopreventive properties it is now available also in dietary supplement form. SFN chemoprevention mechanism include the stimulation of the detoxifying cellular system - the enzymes of II and III metabolism phases. However considered beneficial, it can also alter the medicines metabolism and absorption or lead to development of multidrug resistance (MDR). Due to increasing popularity of dietary supplements the study on SFN influence on drug action is of the increasing importance.

The aim of our study was to determine the influence of SFN on the enzymes of II and III metabolism phases and to evaluate SFN effect on the drug absorption and MDR phenomena.

The SFN influence on activity of quinine reductase (QR) – a surrogate of global II metabolizing phase enzymes was studied in colon cancer Caco-2 cells. Additionally SFN ability to modify the expression of glutathione–S–transferase two isoforms GSTA3, GSTM1 and drug transporters MRP1 and PgP was evaluated by qPCR method . In order to quantify the SFN effect on the intestinal drug absorption a Caco-2 model was developed. SFN effect on the permeability of the three drugs belonging to different BCS group: ketoprofen, verapamil and furosemide was evaluated. Also SFN effect on cytotoxicity of anticancer therapeutic 5-Fluorouracil (5-Fu) was studied. The type of interactions in prostate cell line PC-3 was assessed by Chou-Talaly method.

It was shown that SFN induces QR activity in time and concentration dependent manner. Also II and III metabolism phase enzymes gene expression was altered. We have also shown that the drug permeability was modified by SFN especially in case of furosemide. The effectiveness of 5-Fu was altered in concurrent application with SFN. The study indicates that dietary supplements can interact with cellular metabolizing system and in effect modify the drug action.

 

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Related papers

Presentation: Oral at VIII Multidyscyplinarna Konferencja Nauki o Leku, by Katarzyna Wiktorska
See On-line Journal of VIII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2012-03-15 21:04
Revised:   2012-03-26 20:27