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Modulation of cytochrome P450 isoforms by phenethyl isothiocyanate in rat liver and kidney. |
Hanna M. Szaefer , Violetta K. Krajka-Kuźniak , Wanda Baer-Dubowska |
Poznan University of Medical Sciences, Department of Pharmaceutical Biochemistry, ul. Swiecickiego 4, Poznań 60-781, Poland |
Abstract |
Phenethyl isothiocyanate (PEITC) is one of several compounds from cruciferous vegetables which has raised interest as a potential cancer chemopreventive agent. The anticarcinogenic activity of PEITC has been reported in rodents exposed to a range of initiating agents. PEITC inhibit lung carcinogenesis induced by the tobacco-specific nitrosamines, 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK) in mice and rats, liver tumor by N-nitrosodiethylamine in mice, and esophageal tumor by N-nitrosobenzylmethylamine in rats. As one of the mechanism of chemopreventive activity of PEITC the modulation of CYP isoforms involved in the activation of carcinogens is considered. The administration of PEITC may produce either increase or decrease in CYP content and activity. Our previous studies demonstrated that the i.g. administration of cabbage and sauerkraut juice affected the expression and activity of CYP isozymes. In order to explain to what extent the effect of cabbage is related to PEITC, in this study the activity of CYP1A1, 1A2, 2B1/2, and the expression of CYP1A1/1A2, CYP1B1 and CYP2B1/2 by Western blot were analyzed in Wistar rats liver and kidney. Animals were treated by gavage with PITC for 4, 10 and 30 days. The control group of rats received vehicle only (olive oil). In rat liver treatment with PEITC significantly increased the EROD (the marker of CYP1A1), MROD (the marker of CYP1A2) and PROD (the marker of CYP2B1) activities at all time points of exposure. The most marked effect was observed after 30 days of treatment. In this time point PEITC induced EROD (~2-fold)), MROD and PROD (~3-fold) in comparison with non-treated control. In contrast to the liver, in kidney PEITC did not affect the activity of all enzymes. Among tested CYP isoforms PEITC changed only expression of CYP2B1/2. PEITC increased the level of CYP2B1/2 (by 30%) in liver and to lesser extent in kidney. The correlation between enhanced activity and expression of CYP2B1/2 was found in liver at all time points of exposure. The results of our study indicate that PEITC is responsible for the modulation of CYP isoforms by cabbage, which may play certain role in chemopreventive activity of this product. |
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Presentation: Poster at Zjazd Polskiego Towarzystwa Biochemicznego, Sympozjum G, by Hanna M. SzaeferSee On-line Journal of Zjazd Polskiego Towarzystwa Biochemicznego Submitted: 2007-04-26 12:15 Revised: 2009-06-07 00:44 |