Effects of provitamin A or non-provitamin A carotenoids on liver xenobiotic-metabolizing enzymes in mice.
To determine whether carotenoids can modulate xenobiotic-metabolizing enzymes in mice, catalytic activities of several phase I and phase II enzymes have been measured in liver microsomes and cytosol of male Swiss mice fed diets containing beta-carotene, beta-apo-8'-carotenal, canthaxanthin, or astaxanthin (300 mg/kg diet) or treated with 3-methylcholanthrene (3-MC) (3 times at 50 mg/kg ip) for 15 days. Canthaxanthin increased CYP 1A-dependent activities: ethoxyresorufin O-deethylase (EROD) was increased 3-fold, pentoxyresorufin dealkylase (PROD) was increased 2.5-fold, and methoxyresorufin O-demethylase (MROD) was increased 1.6-fold; these increases were much less than those induced by 3-MC, which induced EROD 49-fold, PROD 10-fold, and MROD 4-fold. 3-MC, but not canthaxanthin, also increased relative liver weight, liver P-450 content, NADH-cytochrome c reductase, and benzoxyresorufin dearylase. The three other carotenoids had little or no effect on phase I enzymes. Among the phase II enzyme activities, only NADPH-quinone reductase was slightly increased by 3-MC and carotenoids, except beta-carotene. Among the three carotenoids that have previously been found to be powerful CYP 1A inducers in the rat, i.e., canthaxanthin, astaxanthin, and beta-apo-8'-carotenal, only canthaxanthin shows some (weak) inducing effect of CYP 1A in the 3-MC-responsive Swiss mice, indicating that the mechanism of CYP 1A induction by carotenoids may not be the same as that by 3-MC. In addition, the fact that beta-carotene has no effect on the tested enzymes does not support the hypothesis that the modulation of xenobiotic metabolism is a possible mechanism for the antimutagenic and anticarcinogenic effects of beta-carotene, which have been demonstrated in several in vivo models in mice.
Astorg
P
P
Unité de Toxicologie Nutritionnelle, Institut National de la Recherche Agronomique, Dijon, France. astorg@dijon.inra.fr
Gradelet
S
S
Leclerc
J
J
Siess
M H
MH
D000818:Animals; D016644:Canthaxanthin / Q000494:pharmacology; D002338:Carotenoids / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D003600:Cytosol / Q000201:enzymology; D004790:Enzyme Induction / Q000187:drug effects; D008099:Liver / Q000201:enzymology*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology; D010088:Oxidoreductases / Q000096:biosynthesis; D014801:Vitamin A / Q000494:pharmacology*; D024341:Xanthophylls; D015262:Xenobiotics / Q000378:metabolism*; D019207:beta Carotene / Q000031:analogs & derivatives / Q000494:pharmacology
D024341:Xanthophylls; D015262:Xenobiotics; D019207:beta Carotene; D014801:Vitamin A; D002338:Carotenoids; D016644:Canthaxanthin; D008748:Methylcholanthrene; C005948:astaxanthine; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; C076307:methoxyresorufin-O-demethylase; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; C004984:apocarotenal