Effects of phenobarbitone and beta-naphthoflavone on hepatic microsomal drug metabolising enzymes of the male beagle dog.
Hepatic microsomes, prepared from male beagle dogs treated with phenobarbitone or beta-naphthoflavone, were compared with microsomes from control dogs and from control, phenobarbitone and beta-naphthoflavone treated rats with respect to various microsomal enzyme activities and for protein profiles generated on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The concentration of total cytochrome P-450 (0.46 nmoles/mg protein) and aldrin epoxidase (0.44 nmoles/mg/min) was lower in control dogs than in the rat, although ethoxycoumarin O-deethylase (ECOD-1.03 nmoles/mg/min) was 2 times and ethoxyresorufin O-deethylase (EROD-0.10 nmoles/mg/min) 5 times higher in the control dogs examined. Possibly as a result of this difference, beta-naphthoflavone induced ECOD 10-fold and EROD 100-fold in the rat, while these enzymes were only increased 3-fold and 5-fold respectively in the two beta-naphthoflavone-treated dogs. Consistent with this, control dog microsomes were found to contain a 58,000 mol. wt protein band that was not present in the SDS-PAGE of control rat microsomes but which was induced in both species by beta-naphthoflavone. Although not identical, the effects of each inducer on the protein profiles were similar in both species. beta-Naphthoflavone produced a marked increase in relative liver weight and, in contrast to published work in the rat, also increased NADPH-cytochrome c reductase levels in the dog. In general, the effects of phenobarbitone were qualitatively and quantitatively similar in both the dog and the rat.
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004285:Dogs; D004790:Enzyme Induction / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D005419:Flavonoids; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; C019647:aldrin epoxidase; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D019363:Cytochrome P-450 CYP1A1; D009251:NADPH-Ferrihemoprotein Reductase; D010634:Phenobarbital