Effects of phenobarbitone and beta-naphthoflavone on hepatic microsomal drug metabolising enzymes of the male beagle dog.

ABSTRACT

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.