Astaxanthin can alter CYP1A-dependent activities via two different mechanisms: Induction of protein expression and inhibition of NADPH P450 reductase dependent electron transfer |
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Authors: | Marumi OhnoWageh S. Darwish Yoshinori IkenakaWataru Miki Mayumi Ishizuka |
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Affiliation: | a Laboratory of Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818, Japan b Graduate School of Science and Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa-shi, Yamagata 992-8510, Japan c Food Control Department, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Ash Sharqiyah Governorate, Egypt |
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Abstract: | 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-containing oil (100 mg Ax/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-, 8.5-, and 2.5-fold, respectively). In contrast, the activities of phase II enzymes (glutathione S-transferase and glucuronosyl-transferase) were not modulated by Ax-containing oil. 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-containing oil 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. |
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Keywords: | Ax, astaxanthin B[a]P, benzo[a]pyrene CYP, cytochrome P450 DCNB, 1,2-dichloro-4-nitrobenzene EROD, ethoxyresorufin O-deethylase GSH, reduced glutathione GST, glutathione S-transferase UDPGA, glucuronic acid trisodium salt UGT, UDP-glucuronosyltransferase |
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