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

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.

α-Tocopherol and Ascorbic Acid Decrease the Production of β-Apo-carotenals and Increase the Formation of Retinoids from β-Carotene in the Lung Tissues of Cigarette Smoke–Exposed Ferrets In Vitro

“…Excentric cleavage oxidative metabolites of ␤-carotene may also be associated with carcinogenesis through their induction of cytochrome P 450 enzymes, which can convert protocarcinogens into activated carcinogens, facilitate lipid peroxidation, or enhance RA catabolism, thereby diminishing retinoid signaling (18). For example, ␤-apo-8Ј-carotenal was shown to be a strong inducer of cytochrome P 450 enzymes (17). Several studies have shown that ␤-apo-carotenals inhibit mitochondria respiration and elevate the accumulation of mal- ondialdehyde in vitro (33,34).…”

Possible roles of excess tryptophan metabolites in cancer

“…Bilrubin was the first endogenous ligand discovered but was very weak in generating AhR-mediated CYP1A1 induction [Sinal and Bend, 1997]. Plant carotinoid indole-3-carbinol was also a potent ligand for AhR [Bjeldanes et al, 1991;Gillner et al, 1993;Gradelet et al, 1996].…”

Induction of liver monooxygenases by annatto and bixin in female rats

“…The rather weak effect of bixin on rat liver monooxygenases belonging to the CYP1A subfamily, on the other hand, indicated that this carotenoid, like ß-carotene, lycopene and lutein, does not share the potent CYP1A1/2-inducing properties of apoor oxocarotenoids such as ß-Apo-8'-carotenal, canthaxanthin and astaxanthin (6,7). The mechanism underlying CYP1A induction by carotenoids is still unclear.…”