Effects of beta-naphthoflavone on the cytochrome P450 system, and phase II enzymes in gilthead seabream (Sparus aurata).
The effect of beta-naphthoflavone (beta-NF) on several catalytic activities of cytochrome P450 (CYP) and phase II enzymes putatively controlled by [Ah]-receptor activation in the liver, heart and kidney of gilthead seabream, was investigated. In the liver, beta-NF treatment [intraperitoneal injection (i.p.) 50 mg/kg] resulted in an increase of CYP content, immunoreactive CYP 1A and methoxyresorufin-O-demethylase (MEROD), pentoxyresorufin O-depentylase (PROD) and ethoxyresorufin-O-deethylase (EROD) activities. However, beta-NF had no effect on any of the hepatic phase II enzymes examined (benzaldehyde dehydrogenase, propionaldehyde dehydrogenase, glutathione S-transferase, UDP-glucuronyl-transferase, DT-diaphorase). Single i.p. injection of 10 mg/kg beta-NF showed a maximal induction of CYP 1A-like protein and EROD activity after 3-7 days. CYP 1A and EROD returned to control levels 18-days post-treatment. beta-NF injection also caused a rapid increase of a single band size of mRNA recognized by a CYP 1A1 cDNA fragment from sea bass (Dicentrarchus labrax). Expression of mRNA preceded the increase of EROD activity and declined rapidly by 96 h. Dose-response experiments demonstrated that EROD was significantly enhanced in liver by a single injection of 0.3 mg/kg beta-NF and was the most sensitive measurement for CYP 1A-like induction. beta-NF treatments also increased the expression of CYP 1A-like protein, mRNA and EROD, but not MEROD and PROD activities in heart and kidney.
Pretti
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Dipartimento di Patologia Animale, Profilassi ed Igiene degli Alimenti, Università di Pisa, V.le delle Piagge 2, 56124, Pisa, Italy. cpretti@vet.unipi.it
Salvetti
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Longo
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Giorgi
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Gervasi
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PG
D000818:Animals; D001711:Biotransformation; D015152:Blotting, Northern; D015153:Blotting, Western; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D012313:RNA / Q000032:analysis / Q000302:isolation & purification; D021541:Sea Bream; D013997:Time Factors; D019324:beta-Naphthoflavone / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D019324:beta-Naphthoflavone; D012313:RNA; D003577:Cytochrome P-450 Enzyme System; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D009251:NADPH-Ferrihemoprotein Reductase; D016660:NAD(P)H Dehydrogenase (Quinone); D005982:Glutathione Transferase