Astaxanthin

beta-Apo-8'-carotenal, but not beta-carotene, is a strong inducer of liver cytochromes P4501A1 and 1A2 in rat.

Gradelet S, Leclerc J, Siess MH, Astorg PO.

Unite de Toxicologie Nutritionnelle, Institut National de la Recherche Agronomique, Dijon, France.

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.

PMID: 8893038 [PubMed - indexed for MEDLINE]