Phenobarbital depression of hepatic microsomal benzo[a]pyrene hydroxylation in rats starved and refed a diet containing menhaden fish oil: substrate and fat level dependency.
The influence of phenobarbital on the activity of hepatic mixed function oxidases responsible for benzo[a]pyrene hydroxylation was studied in rats fed diets containing menhaden fish oil (rich in n-3 fatty acids). Male rats were starved for 2 days and refed diet devoid of fat or containing 0.5, 10, or 20% menhaden oil for 4 days. Phenobarbital increased the apparent Km value as well as Vmax for benzo[a]pyrene hydroxylase in microsomes from rats fed the 20% menhaden oil diet. The increased Km was due to a progressive decrease in benzo[a]pyrene metabolism at the lower substrate concentrations, even in the presence of increased cytochrome P-450 content. The phenobarbital-induced increase in Km and the decreases in benzo[a]pyrene hydroxylation were not observed in rats fed 0.5% menhaden oil or a diet devoid of fat.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000032:analysis*; D001579:Benzopyrene Hydroxylase / Q000032:analysis*; D004041:Dietary Fats / Q000008:administration & dosage*; D005395:Fish Oils / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology*; D010634:Phenobarbital / Q000494:pharmacology*; D011083:Polycyclic Compounds / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D004041:Dietary Fats; D005395:Fish Oils; D011083:Polycyclic Compounds; C033266:Menhaden oil; D008748:Methylcholanthrene; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; D010634:Phenobarbital