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Alterations of the hepatic xenobiotic-metabolizing enzymes by a glucosinolate-rich diet in germ-free rats: influence of a pre-induction with phenobarbital

Published online by Cambridge University Press:  09 March 2007

Sylvie Rabot
Affiliation:
Unité d'Ecologie et de Physiologie du Système Digestif, Centre de Recherches de Jouy, Institut National de la Recherche Agronomique, 78352 Jouy-en-Josas Cedex, France
Lionelle Nugon-Baudon
Affiliation:
Unité d'Ecologie et de Physiologie du Système Digestif, Centre de Recherches de Jouy, Institut National de la Recherche Agronomique, 78352 Jouy-en-Josas Cedex, France
Odette Szylit
Affiliation:
Unité d'Ecologie et de Physiologie du Système Digestif, Centre de Recherches de Jouy, Institut National de la Recherche Agronomique, 78352 Jouy-en-Josas Cedex, France
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Abstract

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Germ-free growing rats were fed on a glucosinolate-rich diet (rapeseed-meal-based) and compared with counterparts fed on a glucosinolate-free diet (soya-bean-meal-based), both diets being isonitrogenous and isoenergetic. For each diet half the animals received phenobarbital in drinking water as an inducer of xenobiotic-metabolizing enzymes. Some of the usual deleterious glucosinolate-linked effects, i.e. kidney hypertrophy and reduction in growth and feed intake, were followed and three of the major hepatic xenobiotic-metabolizing enzymes were investigated. Growth rate, dietary intake and kidney weight were not altered by glucosinolates in the absence of intestinal microflora, whether the animals were treated with phenobarbital or not. As far as the hepatic xenobiotic-metabolizing enzymes are concerned, the specific level of cytochrome P450 and the specific activities of glutathione-S-transferase (EC 2.5.1.18) and UDPglucuronosyltransferase (EC 2.4.1.17) remained unchanged 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 diet. A previous counterpart experiment performed with conventional animals 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 xenobiotic-metabolizing enzymes induced by glucosinolates are somehow mediated by the intestinal microflora. Furthermore, the involvement of those enzymes in glucosinolate toxicity definitely requires the presence of the intestinal microflora.

Type
Nutritional Effects of Biologically Active Components of Plants
Copyright
Copyright © The Nutrition Society 1993

References

REFERENCES

Anon. (1982). Diet Nutrition and Cancer, p. 11. Washington, DC: National Academic Press.Google Scholar
Anon. (1990). Journal Officiel des Communautés Economiqnes Européennes (Official Journal of the EEC). L-170, 28–34.Google Scholar
Bourdon, D.,Perez, J. M. & Baudet, J. J. (1981). Utilisation de nouveaux types de tourteaux de colza par le porc en croissance-finition: influence des glucosinolates et du dépelliculage (New types of rapeseed meal fed to growing-finishing pigs: influence of glucosinolates and dehulling). Journées Recherche Porcine en France 13, 163178.Google Scholar
Conney, A. H. (1982). Induction of microsomal enzymes by foreign chemicals and carcinogenesis by polycyclic aromatic hydrocarbons: G. H. A. Clowes Memorial Lecture. Cancer Research 42, 48754917.Google Scholar
Einarsson, K., Gustafsson, J.-A. & Gustafsson, B. E. (1973). Differences between germ-free and conventional rats in liver microsomal metabolism of steroids. Journal of Biological Chemistry 248, 36233630.CrossRefGoogle ScholarPubMed
Einarsson, K., Gustafsson, J.-A. & Gustafsson, B. E. (1974). Liver microsomal hydroxylation of steroid hormones after establishing an indigenous microflora in germfree rats. Proceedings of the Society for Experimental Biology and Medicine 145, 4852.CrossRefGoogle ScholarPubMed
Greer, M. A. & Astwood, E. B. (1948). The antithyroid effect of certain foods in man as determined with radioactive iodine. Endocrinology 43, 105119.CrossRefGoogle Scholar
Greer, M. A. & Deeney, J. M. (1959). Antithyroid activity elicited by the ingestion of pure progoitrin, a naturally occurring thioglycoside of the turnip family. Journal of Clinical Investigation 38, 14651474.CrossRefGoogle ScholarPubMed
Gustafsson, B. E. & Persson, A. (1975). Reduced sleeping time in germfree rats after pentobarbital administration. In Vth International Symposium on Gnotobiology, pp. 54. Stockholm: Karolinska Institutet.Google Scholar
Habig, W. H., Pabst, M. J. & Jakoby, W. B. (1974). Glutathione-S-transferases – The first enzymatic step in mercapturic acid formation. Journal of Biological Chemistry 249, 22, 71307139.CrossRefGoogle ScholarPubMed
Hietanen, E. & Pelkonen, K. (1979). Hepatic and extrahepatic induction of drug-metabolizing enzymes in specific pathogen free and germ free rats. General Pharmacology 10, 239247.CrossRefGoogle ScholarPubMed
Langer, P., Michajlovskij, N., Sedlak, J. & Kutka, M. (1971). Studies on the antithyroid activity of naturally occurring L-5-vinyl-2-thiooxazolidone. Endokrinologie 57, 225229.Google ScholarPubMed
Lowry, O. H., Rosebrough, N. J., Farr, A. L. & Randall, R. J. (1951). Protein measurement with the Fohn phenol reagent. Journal of Biological Chemistry 193, 265275.CrossRefGoogle Scholar
McDanell, R. E. & McLean, A. E. M. (1984). Differences between small and large intestine and liver in the inducibility of microsomal enzymes in response to stimulation by phenobarbitone and betanaphtoflavone in the diet. Biochemical Pharmacology 33, 19771980.CrossRefGoogle Scholar
McDanell, R. E., McLean, A. E. M., Hanky, A. B., Heaney, R. K. & Fenwick, G. R. (1989). The effect of feeding Brassica vegetables and intact glucosinolates on mixed-function-oxydase activity in the livers and intestines of rats. Food and Chemical Toxicology 27, 289293.CrossRefGoogle Scholar
McMillan, M., Spinks, E. A. & Fenwick, G. R. (1986). Preliminary observations on the effect of dietary brussels sprouts on thyroid function. Human Toxicology 5, 1519.CrossRefGoogle ScholarPubMed
Martland, M. F., Butler, E. J. & Fenwick, G. R. (1984). Rapeseed induced liver haemorrhage, reticulolysis and biochemical changes in laying hens: the effects of feeding high and low glucosinolate meals. Research in Veterinary Science 36, 298309.CrossRefGoogle ScholarPubMed
Michajlovskij, N., Sedlak, J., Jusic, M. & Buzina, R. (1969). Goitrogenic substances of kale and their possible relations to the endemic goitre on the island of Krk (Yugoslavia). Endocrinologia Experimentalis 3, 6572.Google Scholar
Miller, K. W. & Stoewsand, G. S. (1983). Hepatic polysubstrate monooxygenase activities in different strains of rats fed cabbage (Brassica oleracea). Drug and Chemical Toxicology 6, 93110.CrossRefGoogle ScholarPubMed
Mitjavila, S. (1986). Substances naturelles nocives des aliments (Natural toxicants occurring in food). In Toxicologie et Sécurité des Aliments, pp. 129157 [Derache, R., editor]. Paris: Lavoisier et Apria.Google Scholar
Mizutani, T. & Mitsuoka, T. (1988). Effect of dietary phenobarbital on spontaneous hepatic tumorigenesis in germfree C3H/He male mice. Cancer Letters 39, 233237.CrossRefGoogle ScholarPubMed
Nugon-Baudon, L., Rabot, S., Szylit, O. & Raibaud, P. (1990). Glucosinolates toxicity in growing rats: interactions with the hepatic detoxication system. Xenobiorica 20, 223230.CrossRefGoogle Scholar
Nugon-Baudon, L., Szylit, O. & Raibaud, P. (1988). Production of toxic glucosinolate derivatives from rapeseed meal by intestinal microflora of rat and chicken. Journal of the Science of Food and Agriculture 43, 299308.CrossRefGoogle Scholar
Omura, T. & Sato, R. (1964). The carbon monoxide-binding pigment of liver microsomes I. Evidence for its hemoprotein nature. Journal of Biological Chemistry 239, 23702378.CrossRefGoogle ScholarPubMed
Ryan, D., Lu, A. Y. H. & Levin, W. (1978). Purification of cytochrome P450 and P448 from rat liver microsomes. Methods in Enzymology 52, 117123.CrossRefGoogle ScholarPubMed
Singh, J. & Wiebel, F. J. (1979). A highly sensitive and rapid fluorometric assay for UDP-glucuronyltransferase using 3-hydroxybenzo(a)pyrene as substrate. Analytical Biochemistry 98, 394401.CrossRefGoogle ScholarPubMed
Snedecor, G. W. & Cochran, W. G. (1967). Statistical Methods, 6th ed. Ames, Iowa: Iowa State University Press.Google Scholar
Stoewsand, G. S., Anderson, J. L. & Munson, L. (1988). Protective effect of dietary Brussels sprouts against mammary carcinogenesis in Sprague-Dawley rats. Cancer Letters 39, 199207.CrossRefGoogle ScholarPubMed
Stoewsand, G. S., Babish, J. B. & Wimberley, H. C. (1978). Inhibition of hepatic toxicities from polybrominated biphenyls and aflatoxine B, in rats fed cauliflower. Journal of Environmental Pathology and Toxicology 2, 399406.Google ScholarPubMed
Ullrich, D. & Bock, K. W. (1984). Glucuronide formation of various drugs in liver microsomes and in isolated hepatocytes from phenobarbital- and 3-methylcholanthrene-treated rats. Biochemical Pharmacology 33, 97101.CrossRefGoogle ScholarPubMed
Vermorel, M., Davicco, M. J. & Evrard, J. (1987). Valorization of rapeseed meal. 3. Effects of glucosinolate content on food intake, weight gain, liver weight and plasma thyroid hormone levels in growing rats. Reproduction Nutrition Développement 27, 5766.CrossRefGoogle ScholarPubMed
Wattenberg, L. W. (1971). Studies of polycyclic hydrocarbon hydroxylases of the intestine possibly related to cancer. Effect of diet on benzpyrene hydroxylase activity. Cancer 28, 99102.3.0.CO;2-M>CrossRefGoogle ScholarPubMed
Young, W. S. III & Lietman, P. S. (1978). Chloramphenicol glucuronyltransferase: assay, ontogeny and inducibility. Journal of Pharmacology and Experimental Therapeutics 204, 203211.Google ScholarPubMed