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Title
  • en Astaxanthin can alter CYP1A-dependent activities via two different mechanisms : Induction of protein expression and inhibition of NADPH P450 reductase dependent electron transfer
Creator
    • en Ohno, Marumi
    • en Darwish, Wageh S.
    • en Miki, Wataru
Accessrights open access
Subject
  • Other en Astaxanthin
  • Other en Cytochrome P450 1A
  • Other en Conjugating enzyme
  • Other en Metabolic activation
  • Other en Benzo[a]pyrene
  • Other en NADPH P450 reductase
  • NDC 498
Description
  • Abstract en Astaxanthin (Ax), a xanthophyll carotenoid, is reported to induce cytochrome P450 (CYP) 1A-dependent activity. CYP1A is one of the most important enzymes participating in phase I metabolism for chemicals, and it can activate various mutagens. To investigate the effect of Ax on the metabolic activation of a typical promutagen, benzo[a]pyrene by CYP1A, we orally administrated Ax (100 mg / kg body weight / day for 3 days) to male Wistar rats. In the treated rat liver, expression of CYP1A1 mRNA, protein, and its activity were significantly increased (5.5-fold, 8.5-fold, and 2.5-fold, respectively). In contrast, the activities of phase II enzymes (glutathione S-transferase and glucuronosyl-transferase) were not modulated by Ax. As a consequence, the mutagenicity of benzo[a]pyrene was more enhanced in Ax-treated rats, compared with controls in the Ames assay. On the other hand, NADPH P450 reductase activity was decreased in liver microsomes from the treated group. This result suggests the possibility that Ax inhibits the electron supply necessary for CYP catalytic activities and decreases CYP1A activity indirectly. In conclusion, Ax intake can alter CYP1A-dependent activities through two different mechanisms: 1) induction of CYP1A1 mRNA, protein expression, and activity; and 2) inhibition of the electron supply for the enzyme.
Publisher en Elsevier
Date
    Issued2011-06
Language
  • eng
Resource Type journal article
Version Type AM
Identifier HDL http://hdl.handle.net/2115/46205
Relation
  • isVersionOf DOI https://doi.org/10.1016/j.fct.2011.03.009
  • PMID 21414371
Journal
    • PISSN 0278-6915
      • en Food and Chemical Toxicology
      • Volume Number49 Issue Number6 Page Start1285 Page End1291
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Oaidate 2023-07-26