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

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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 β-carotene isomers (all-trans β-carotene or β-carotene from Dunaliella salina rich in 9-cis isomer or isomerized β-carotene), or apocarotenoids as β-apo-8′-carotenal, ethyl β-apo-8′-carotenoate and citranaxanthin. 2. β-carotene, either all-trans or containing cis isomers, did not induce any significant change in the measured activities. By contrast, β-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 (x 22), 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 β-apo-8′-carotenal. Western blots of microsomal proteins clearly showed the induction of CYP1A1 and 1A2 by β-apo-8′-carotenal. This induction profile resembles that produced by two other carotenoids: canthaxanthin and astaxanthin. Ethyl β-apo-8′-carotenoate and citranaxanthin showed similar effects to β-apo-8′-carotenal but of less intensity. 3. Three carotenoids: β-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, β-naphtoflavone or dioxin.