Interaction of carbon tetrachloride with beta-naphthoflavone-mediated cytochrome P450 induction in winter flounder (Pseudopleuronectes americanus).
The interaction between beta-naphthoflavone induction (BNF: 100 mg/kg) and carbon tetrachloride (CCl4; 1 ml/kg) hepatotoxicity was examined in the flounder. Treatment groups composed of control, BNF, CCl4, and BNF/CCl4 were compared in terms of cytochrome P450 isozyme content (LM4b; LM2), catalytic activity, isozyme distribution. SGOT-SGPT levels, and pathology. CCl4 administration resulted in significant reductions in both the constitutive P450 (LM2) and the BNF-inducible isozyme (LM4b) as well as elevations in SGPT and SGOT levels. The decline in LM4b isozyme content was reflected by stoichiometric decreases in ethoxyresorufin-O-deethylase activities. BNF/CCl4 coadministration was protective in part against CCl4 hepatotoxicity. Immunohistochemistry indicated that LM4b was diffusely distributed throughout the liver. These interactions have demonstrated a multiple P450 isozyme involvement, the protective nature of BNF against CCl4 hepatotoxicity in the flounder, the ability to maintain an inductive response in face of CCl4 coadministration, and the diffuse distributional pattern of LM4b in the flounder liver.
Kleinow
K M
KM
Department of Veterinary Physiology, School of Veterinary Medicine, Louisiana State University, Baton Rouge 70803.
Droy
B F
BF
Buhler
D R
DR
Williams
D E
DE
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001571:Benzoflavones / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000037:antagonists & inhibitors / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D005432:Flounder; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008853:Microscopy / Q000379:methods; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D005419:Flavonoids; D007527:Isoenzymes; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase