title: Characterization of the temporal induction of hepatic xenobiotic-metabolizing enzymes by glucosinolates and isothiocyanates: requirement for at least a 6 h exposure to elicit complete induction profile.
abstract: A mechanism of action of chemopreventive glucosinolates/isothiocyanates, established largely in vitro, is to modulate carcinogen-metabolizing enzymes. Extrapolation in vivo involves relating in vitro concentrations to plasma/tissue concentrations attained in vivo, thus assuming that even transient exposure modulates enzyme activity. To test this hypothesis, precision-cut rat liver slices were incubated with glucosinolates for up to 24 h, and the O-dealkylation of methoxyresorufin and ethoxyresorufin was determined; increased activities were observed only at incubations of at least 6 h. To evaluate phase II enzymes, isothiocyanates, namely, sulforaphane, erucin, and phenethyl isothiocyanate, were similarly incubated; quinone reductase increased after incubation for 6 h or longer. When glutathione S-transferase was monitored, the phenethyl isothiocyanate-manifested rise necessitated at least a 6 h incubation, whereas in the case of sulforaphane and erucin, the activity was elevated after only 2 h. It is inferred that a rise in carcinogen-metabolizing enzymes by glucosinolates/isothiocyanates necessitates tissue exposure of at least 6 h.
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United Kingdom.
authors.forename: Ahmad F Abdull
authors.initials: AF
authors.lastname: Razis
authors.forename: Manuela
authors.initials: M
authors.lastname: Bagatta
authors.forename: Gina R
authors.initials: GR
authors.lastname: De Nicola
authors.forename: Renato
authors.initials: R
authors.lastname: Iori
authors.forename: Nick
authors.initials: N
authors.lastname: Plant
authors.forename: Costas
authors.initials: C
authors.lastname: Ioannides
mesh_terms: D000818:Animals; D005961:Glucosinolates / Q000378:metabolism*; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D017879:Isothiocyanates / Q000378:metabolism*; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D015854:Up-Regulation; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D005961:Glucosinolates; D017879:Isothiocyanates; D015262:Xenobiotics; D016660:NAD(P)H Dehydrogenase (Quinone); D005982:Glutathione Transferase