Influence of intact and myrosinase-treated indolyl glucosinolates on the metabolism in vivo of metronidazole and antipyrine in the rat.
Induction of the cytochrome P-450 enzymes is a mechanism whereby cruciferous vegetables and their glucosinolates could influence the risk of cancer. The cytochrome P-450-inducing capacity of isolated intact broccoli glucosinolates and their degradation products, resulting from myrosinase-catalysed hydrolysis, has been assessed in studies of the metabolism of antipyrine (AP) and metronidazole (MZ) in the rat. The intact glucosinolates had no effect on the metabolism of MZ and AP as measured by the clearance and metabolite formation rates; however, the myrosinase-treated glucosinolates significantly increased the clearance of AP by two-thirds and the formation rates of the three major AP metabolites by 87-100%, and doubled the rate of oxidative metabolism of MZ to its hydroxy and acetic acid metabolites. Active myrosinase was thus essential for the capacity of glucosinolates from broccoli (mainly indolyl glucosinolates) to induce the activity of several cytochrome P-450 isoenzymes involved in the metabolism of AP and MZ. The data indicated that hydrolysis products of indolyl glucosinolates had an inducing effect on the activity, but not the total amount, of hepatic cytochrome P-450 isoenzymes. The effect of these products on the oxidative metabolism of AP and MZ was similar to that of phenobarbital. The significance of this induction pattern in relation to cancer risk depends primarily on the activation/inactivation mechanism of the relevant carcinogen.
Loft
S
S
Department of Pharmacology, University of Copenhagen, Denmark.
Otte
J
J
Poulsen
H E
HE
Sørensen
H
H
D000818:Animals; D000983:Antipyrine / Q000378:metabolism* / Q000493:pharmacokinetics; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D005961:Glucosinolates / Q000494:pharmacology*; D006026:Glycoside Hydrolases / Q000494:pharmacology*; D006868:Hydrolysis; D007211:Indoles / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis*; D008099:Liver / Q000033:anatomy & histology / Q000201:enzymology; D008297:Male; D008795:Metronidazole / Q000378:metabolism* / Q000493:pharmacokinetics; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D005961:Glucosinolates; D007211:Indoles; D007527:Isoenzymes; D008795:Metronidazole; D003577:Cytochrome P-450 Enzyme System; D006026:Glycoside Hydrolases; C022739:thioglucosidase; D000983:Antipyrine