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Black cabbage seed extract affects rat Cyp-mediated biotransformation: Organ and sex related differences
Authors:Donatella Canistro  Jessica Barillari  Simone Melega  Andrea Sapone  Renato Iori  Ester Speroni  Moreno Paolini
Affiliation:1. Department of Pharmacology, Molecular Toxicology Unit, Alma Mater Studiorum-University of Bologna, Via Irnerio 48, 40126 Bologna, Italy;2. Agricultural Research Council – Research Center for Industrial Crops (CRA-CIN), Via di Corticella 133, 40128 Bologna, Italy
Abstract:Brassicaceae are widely consumed in many parts of the world and their dietary intake has been associated with cancer risk reduction. Extracts and metabolites derived from cruciferous vegetables have thus gained popularity as potential cancer chemopreventive agents. We have previously found, unexpectly, that glucoraphanin, the most extensively present glucosinolate in these vegetables, is a potent mutagen bioactivating Phase-I enzyme inducer. In the present study, the influence of black cabbage seed extract, rich in glucoraphanin, was investigated on Phase-I enzymes in different organs of male or female rats. Oral seed extract injection at 120 or 240 mg/kg b.w. for one or four consecutive days, significantly affected various cytochrome P450 (CYP) –linked monooxygenases in a complex way being the lung the most responsive organ (in males, up to ∼2600% increase for CYP2B1/2 isoform and ∼96% loss for CYP1A1, CYP3A1/2). These findings indicate that the extract may strongly enhance and/or suppress rat xenobiotic biotransformation pathways and that caution should be paid to the possible influence on human metabolism. These data suggest an overall evaluation of the balance between beneficial vs. possible adverse effects for each agent, even if of natural origin, prior to routinely, preventive mass use.
Keywords:CYP, cytochrome P450   GRA, glucoraphanin   GL, glucosinolates   BCSE, black cabbage seed extract   MFO, mixed function oxidase activity   CYP-red, NADPH-(CYP)-c-reductase   APND, aminopyrine N-demethylase   pNFH, p-nitrophenol hydroxylase   PROD, pentoxyresorufin O-dealkylase   EROD, ethoxyresorufin O-deethylase   MROD, methoxyresorufin O-demethylase   ECOD, ethoxycoumarin O-deethylase   TH, testosterone hydroxylase
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