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β-Apo-8′-carotenal, but notβ-carotene, is a strong inducer of liver cytochromes P4501A1 and 1A2 in rat

 

作者: GradeletS.,   LeclercJ.,   H.M,   AstorgP. O.,  

 

期刊: Xenobiotica  (Taylor Available online 1996)
卷期: Volume 26, issue 9  

页码: 909-919

 

ISSN:0049-8254

 

年代: 1996

 

DOI:10.3109/00498259609052493

 

出版商: Taylor&Francis

 

数据来源: Taylor

 

摘要:

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/kgβ-carotene isomers (all-transβ-carotene orβ-carotene fromDunaliella salinarich in 9-cisisomer or isomerizedβ-carotene), or apocarotenoids asβ-apo-8′-carotenal, ethylβ-apo-8′-carotenoate and citranaxanthin.2.β-carotene, either all-transor containingcisisomers, 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 ethoxyresorufinO-deethylase (x158), methoxyresorufinO-demethylase (x 22), pentoxy- and benzoxyresorufinO-dealkylases, but did not affect erythromycinN-demethylase nor nitrosodimethylamineN-demethylase activities. Phase IIp-nitrophenol- and 4-hydroxy-biphenyl-uridine diphosphoglucuronosyl transferase activities were also increased byβ-apo-8′-carotenal. Western blots of microsomal proteins clearly showed the induction of CYP1A1 and 1A2 byβ-apo-8′-carotenal. This induction profile resembles that produced by two other carotenoids: canthaxanthin and astaxanthin. Ethylβ-apo-8′-carotenoate and citranaxanthin showed similar effects toβ-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.

 

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