Intact glucosinolates modulate hepatic cytochrome P450 and phase II conjugation activities and may contribute directly to the chemopreventive activity of cruciferous vegetables.
The currently accepted view is that the chemopreventive activity of glucosinolates is exclusively mediated by their degradation products, such as isothiocyanates. In the present study, evidence is presented for the first time that intact glucosinolates can modulate carcinogen-metabolising enzyme systems. The glucosinolates glucoraphanin and glucoerucin were isolated from cruciferous vegetables and incubated with precision-cut rat liver slices. Both glucosinolates elevated the O-dealkylations of methoxy- and ethoxyresorufin, markers for CYP1 activity; supplementation of the incubation medium with myrosinase, the enzyme that converts glucosinolates to their corresponding isothiocyanates, abolished these effects. Moreover, both glucoerucin and glucoraphanin increased the apoprotein levels of microsomal CYP1A1, CYP1A2 and CYP1B1. At higher concentrations, both glucosinolates enhanced quinone reductase activity, whereas glucoraphanin also elevated glutathione S-transferase; in this instance, however, supplementation of the incubation medium with myrosinase exacerbated the inductive effect. Finally, both glucosinolates increased modestly cytosolic quinone reductase, GSTα and GSTμ protein levels, which became more pronounced when myrosinase was added to the incubations with the glucosinolate. It may be inferred that intact glucosinolates can modulate the activity of hepatic carcinogen-metabolising enzyme systems and this is likely to impact on the chemopreventive activity linked to cruciferous vegetable consumption.
Abdull Razis
Ahmad F
AF
Molecular Toxicology Group, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU27XH, UK.
Bagatta
Manuela
M
De Nicola
Gina R
GR
Iori
Renato
R
Ioannides
Costas
C
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D019607:Brassicaceae / Q000187:drug effects / Q000235:genetics; D018890:Chemoprevention; D003227:Conjugation, Genetic / Q000187:drug effects*; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D019388:Cytochrome P-450 CYP1A2; D065633:Cytochrome P-450 CYP1B1; D003580:Cytochromes / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D005961:Glucosinolates / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010936:Plant Extracts / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012639:Seeds; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D014675:Vegetables / Q000187:drug effects / Q000235:genetics
D003580:Cytochromes; D005961:Glucosinolates; D010936:Plant Extracts; D001189:Aryl Hydrocarbon Hydroxylases; C017170:Cyp1a2 protein, rat; C585499:Cyp1b1 protein, rat; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D065633:Cytochrome P-450 CYP1B1