Hexachlorobenzene-induced porphyria in Japanese quail. Effect of pretreatment with phenobarbital or beta-naphthoflavone.
In an effort to determine the role that metabolism by the cytochrome P-450 system plays in the development of hexachlorobenzene (HCB)-induced porphyria, Japanese quail were pretreated with either beta-naphthoflavone (BNF) or phenobarbital (PB) and then treated with HCB. PB or BNF pretreatment appeared to have no effect on the response of quail hepatic enzymes to HCB. There were no differences between the two groups in either the content of cytochrome P-450 or the activities of NADPH-cytochrome c reductase, glutathione transferase (microsomal or cytosolic), ethoxycoumarin-O-deethylase or ethoxyresorufin-O-deethylase following HCB treatment. These pretreatments did, however, markedly influence the development of porphyria in quail. BNF-treated birds had higher delta-aminolevulinic acid-synthetase (ALA-S) activities and developed porphyria much more rapidly than birds treated with HCB alone. Birds pretreated with PB did not exhibit porphyria even following 10 days of HCB. Although the ALA-S activities in this group were elevated slightly following HCB, they were about one-half of those seen in the BNF-pretreated HCB-treated group. These results may reflect a difference between the PB and BNF groups in the production of a porphyrogenic metabolite of HCB.
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology*; D002722:Chlorobenzenes / Q000633:toxicity*; D003370:Coturnix; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D005419:Flavonoids / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism; D006581:Hexachlorobenzene / Q000633:toxicity*; D008099:Liver / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology*; D011164:Porphyrias / Q000139:chemically induced / Q000201:enzymology*; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D002722:Chlorobenzenes; D005419:Flavonoids; D006581:Hexachlorobenzene; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D019363:Cytochrome P-450 CYP1A1; D009251:NADPH-Ferrihemoprotein Reductase; D005982:Glutathione Transferase; D010634:Phenobarbital