Coumarin-induced changes in delta-aminolaevulinic acid synthase and cytochrome P-450 in chick embryo liver.
Coumarin occurs naturally in the diet and inhibits several cytochrome P-450 enzymes in laboratory animals. The effect of coumarin was examined on haem biosynthesis and cytochrome P-450 activities in the 18-day-old chick embryo liver in ovo. At 40 and 50 mumol/embryo coumarin increased delta-aminolaevulinic acid synthase, porphyrins, cytochrome P-450, benzphetamine N-demethylase and benzo[a]pyrene hydroxylase. At 10 mumol/embryo coumarin decreased aniline 4-hydroxylase, and at both 10 and 50 mumol/embryo it decreased 7-ethoxyresorufin O-deethylase, coumarin 7-hydroxylase and nitrosodimethylamine N-demethylase. 7-Hydroxycoumarin and 5, 7-methoxycoumarin at 40 mumol/embryo had none of these effects. Coumarin (5-500 microM) added to liver microsomes inhibited aniline hydroxylase by 45%, but not nitrosodimethylamine N-demethylase, and inhibited 7-ethoxyresorufin O-deethylase in microsomes from 3-methylcholanthrene-treated embryos by 15 and 100% at coumarin concentrations of 250 and 500 microM, respectively. Coumarin 7-hydroxylase activity in chick embryo liver was comparable with that reported for human liver and greater than in the rat. The data indicate that coumarin can both increase and decrease cytochrome P-450 activities in chick embryo liver and can induce haem biosynthesis. Because the chick embryo liver hydroxylates coumarin at position 7 in a manner similar to humans, it may be a more suitable model than the rat for studying some of the metabolic effects of coumarin.
Goeger
D E
DE
Department of Preventive Medicine & Community Health, University of Texas Medical Branch, Galveston 77550.
Anderson
K E
KE
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism*; D000815:Aniline Hydroxylase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001579:Benzopyrene Hydroxylase / Q000187:drug effects / Q000378:metabolism; D002642:Chick Embryo; D003374:Coumarins / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1; D065637:Cytochrome P-450 CYP2A6; D019392:Cytochrome P-450 CYP2E1; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D006418:Heme / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology; D008861:Microsomes / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000187:drug effects / Q000378:metabolism; D010088:Oxidoreductases / Q000187:drug effects / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000187:drug effects / Q000378:metabolism; D011166:Porphyrins / Q000378:metabolism
D003374:Coumarins; D065607:Cytochrome P-450 Enzyme Inhibitors; D011166:Porphyrins; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; C030123:coumarin; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D019392:Cytochrome P-450 CYP2E1; D000815:Aniline Hydroxylase; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D065637:Cytochrome P-450 CYP2A6; C019781:benzphetamine N-demethylase; D010089:Oxidoreductases, N-Demethylating; D000624:5-Aminolevulinate Synthetase