ALTERATIONS OF THE HEPATIC XENOBIOTIC-METABOLIZING ENZYMES BY A GLUCOSINOLATE-RICH DIET IN GERM-FREE RATS - INFLUENCE OF A PREINDUCTION WITH PHENOBARBITAL

Germ-free growing rats were fed on a glucosinolate-rich diet (rapeseed -meal-based) and compared with counterparts fed on a glucosinolate-fre e diet (soya-bean-meal-based), both diets being isonitrogenous and iso energetic. For each diet half the animals received phenobarbital in dr inking water as an inducer of xenobiotic-metabolizing enzymes. Some of the usual deleterious glucosinolate-linked effects, i.e. kidney hyper trophy and reduction in growth and feed intake, were followed and thre e of the major hepatic xenobiotic-metabolizing enzymes were investigat ed. Growth rate, dietary intake and kidney weight were not altered by glucosinolates in the absence of intestinal microflora, whether the an imals were treated with phenobarbital or not. As far as the hepatic xe nobiotic-metabolizing enzymes are concerned, the specific level of cyt ochrome P450 and the specific activities of glutathione-S-transferase (EC 2.5.1.18) and UDPglucuronosyltransferase (EC2.4.1.17) remained unc hanged in rats receiving the glucosinolate-rich diet compared with the control animals. Despite the low dose given, phenobarbital displayed its usual inducing effect on all three enzymes, similar whatever the d iet. A previous counterpart experiment performed with conventional ani mals had shown that glucosinolate feeding led to large alterations of the variables herein studied, some of these modifications being hugely enhanced by a phenobarbital treatment. Therefore, the present results obtained on germ-free animals prove that alterations of the xenobioti c-metabolizing enzymes induced by glucosinolates are somehow mediated by the intestinal microflora. Furthermore, the involvement of those en zymes in glucosinolate toxicity definitely requires the presence of th e intestinal microflora.