beta-Apo-8'-carotenal, but not beta-carotene, is a strong inducer of liver cytochromes P4501A1 and 1A2 in rat.
1. The catalytic activities of several phase I and II xenobiotic-metabolizing enzymes and their immunochemical detection have been investigated in liver microsomes and cytosol of the male rat, which had been fed for 15 days with diets containing 300 mg/kg beta-carotene isomers (all-trans beta-carotene or beta-carotene from Dunaliella salina rich in 9-cis isomer or isomerized beta-carotene), or apocarotenoids as beta-apo-8'-carotenal, ethyl beta-apo-8'-carotenoate and citranaxanthin. 2. Beta-carotene, either all-trans or containing cis isomers, did not induce any significant change in the measured activities. By contrast, beta-apo-8'-carotenal increased the liver content of cytochrome P450, the activity of NADH- and NADPH-cytochrome c reductase, and strongly increased some cytochrome P450-dependent activities, particularly ethoxyresorufin O-deethylase (x158), methoxyresorufin O-demethylase (x22), pentoxy- and benzoxyresorufin O-dealkylases, but did not affect erythromycin N-demethylase nor nitrosodimethylamine N-demethylase activities. Phase II p-nitrophenol- and 4-hydroxy- biphenyl-uridine diphosphoglucuronosyl transferase activities were also increased by beta-apo-8'carotenal. Western blots of microsomal proteins clearly showed the induction of CYP1A1 and 1A2 by beta-apo-8'-carotenal. This induction profile resembles that produced by two other carotenoids: canthaxanthin and astaxanthin. Ethyl beta-apo-8'-carotenoate and citranaxanthin showed similar effects to beta-apo-8'-carotenal but of less intensity. 3. Three carotenoids: beta-apo-8'-carotenal, canthaxanthin and astaxanthin, are inducers of CYP1A1 and 1A2 in the rat. These carotenoids form a new class of inducers of CYP1A, structurally very different from the classical inducers as 3-methylcholanthrene, beta-naphtoflavone or dioxin.
Unité de Toxicologie Nutritionnelle, Institut National de la Recherche Agronomique, Dijon, France.
S
S
Gradelet
J
J
Leclerc
M H
MH
Siess
P O
PO
Astorg
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D016644:Canthaxanthin / Q000494:pharmacology; D002338:Carotenoids / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D004435:Eating / Q000187:drug effects; D004790:Enzyme Induction; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019207:beta Carotene / Q000494:pharmacology*
D000975:Antioxidants; D019207:beta Carotene; D002338:Carotenoids; D016644:Canthaxanthin; D008748:Methylcholanthrene; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D009251:NADPH-Ferrihemoprotein Reductase; C004984:apocarotenal