title: Effects of beta-naphthoflavone on hepatic biotransformation and glutathione biosynthesis in largemouth bass (Micropterus salmoides).
abstract: We are investigating the effects of in vivo exposure of prototypical enzyme inducing agents on hepatic biotransformation enzyme expression in largemouth bass (Micropterus salmoides), a predatory game fish found throughout the United States and Canada. The current study targeted those genes involved in biotransformation and oxidative stress that may be regulated by Ah-receptor-dependent pathways. Exposure of bass to beta-naphthoflavone (beta-NF, 66 mg/kg, i.p.) elicited a 7-9-fold increase in hepatic microsomal cytochrome P4501A-dependent ethoxyresorufin O-deethylase (EROD) activities, but did not affect cytosolic GST catalytic activities toward 1-chloro-2,4-dinitrobenzene (CDNB) or 5-androstene-3,17-dione (ADI). Glutathione S-transferase A (GST-A) mRNA expression exhibited a transient, but non-significant increase following exposure to beta-NF, and generally tracked the minimal changes observed in GST-CDNB activities. Expression of the mRNA encoding glutamate-cysteine ligase catalytic subunit (GCLC), the rate-limiting enzyme in glutathione (GSH) biosynthesis, was increased 1.7-fold by beta-NF. Changes in GCLC mRNA expression were paralleled by increases in intracellular GSH. In summary, largemouth bass hepatic CYP1A-dependent and GSH biosynthetic pathways, and to a lesser extent GST, are responsive to exposure to beta-NF.
authors.affiliation: Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, P.O. Box 110885, Gainesville, FL 32611-0885, USA.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Hughes
authors.forename: Evan P
authors.initials: EP
authors.lastname: Gallagher
mesh_terms: D000704:Analysis of Variance; D000735:Androstenedione; D000818:Animals; D001492:Bass / Q000378:metabolism*; D001711:Biotransformation / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D004137:Dinitrochlorobenzene; D004790:Enzyme Induction / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000096:biosynthesis / Q000235:genetics; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000201:enzymology; D008861:Microsomes / Q000201:enzymology; D010957:Plasmids / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism*; D019324:beta-Naphthoflavone / Q000493:pharmacokinetics* / Q000633:toxicity*
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D004137:Dinitrochlorobenzene; D012333:RNA, Messenger; D000735:Androstenedione; C003528:5-androstene-3,17-dione; D019324:beta-Naphthoflavone; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione