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

Xenobiotica. 1996 Sep;26(9):909-19. doi: 10.3109/00498259609052493.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Body Weight / drug effects
  • Canthaxanthin / pharmacology
  • Carotenoids / pharmacology*
  • Cytochrome P-450 CYP1A1 / metabolism*
  • Cytochrome P-450 CYP1A2 / metabolism*
  • Eating / drug effects
  • Enzyme Induction
  • Liver / drug effects
  • Liver / enzymology*
  • Male
  • Methylcholanthrene / pharmacology
  • Microsomes, Liver / enzymology
  • NADPH-Ferrihemoprotein Reductase / metabolism
  • Rats
  • Rats, Wistar
  • beta Carotene / pharmacology*

Substances

  • Antioxidants
  • beta Carotene
  • Carotenoids
  • Canthaxanthin
  • Methylcholanthrene
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP1A2
  • NADPH-Ferrihemoprotein Reductase
  • apocarotenal