Food Chem Toxicol. 1991 Mar;29(3):145-51.  

Coumarin-induced changes in delta-aminolaevulinic acid synthase and cytochrome
P-450 in chick embryo liver.

Goeger DE, Anderson KE.

Department of Preventive Medicine & Community Health, University of Texas
Medical Branch, Galveston 77550.

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.

PMID: 2032655 [PubMed - indexed for MEDLINE]