title: Modulation of cytochrome P-450 and glutathione S-transferase isoform expression in vivo by intact and degraded indolyl glucosinolates.
abstract: Various dietary substances modulate the xenobiotic metabolism and may thereby protect against toxicity and carcinogenicity of food toxins. The effects of pure indolyl glucosinolates, which are present in cruciferous vegetables, on induction of specific cytochrome P-450 (CYP) and glutathione S-transferase (GST) isoforms have not been studied previously. In the present study, glucobrassicin (GB) and neoglucobrassicin (NeoGB) were purified from broccoli by use of a single-column method. Furthermore, a mixture containing 48% GB, 36% NeoGB, and 16% 4-methoxyglucobrassicin was obtained. The modulatory effects of the pure GB, NeoGB, and the mixture on activities and levels of hepatic CYP 1A, 2B1/2, and 2E1 and alpha- and mu-GST isoforms were investigated in male Wistar rats. The indolyl mixture was the most powerful and NeoGB the weakest inducer of microsomal hepatic CYP 1A1 protein and 7-ethoxyresorufin O-deethylase activity. Furthermore, intact indolyl glucosinolates were more powerful inducers than the in vitro myrosinase-degraded indolyl glucosinolates. The hepatic 7-methoxyresorufin O-deethylase activities, but not CYP 1A2 protein, were induced by pure GB, whereas the mixture and NeoGB showed only minor effects. Neither CYP 2B1/2 nor 2E1 was induced by the indolyl glucosinolates. None of the hepatic GST subunits analyzed, rGST A1/2, A3, or M3, was induced significantly by the purified indolyl glucosinolates.
authors.affiliation: Department of Life Sciences and Chemistry, Roskilde University, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Bonnesen
authors.forename: P U
authors.initials: PU
authors.lastname: Stephensen
authors.forename: O
authors.initials: O
authors.lastname: Andersen
authors.forename: H
authors.initials: H
authors.lastname: Sørensen
authors.forename: O
authors.initials: O
authors.lastname: Vang
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D005961:Glucosinolates / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000187:drug effects* / Q000378:metabolism; D007211:Indoles; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016588:Anticarcinogenic Agents; D005961:Glucosinolates; D007211:Indoles; D003577:Cytochrome P-450 Enzyme System; C048308:glucobrassicin; D005982:Glutathione Transferase