Dietary fat--a requirement for induction of mixed-function oxidase activities in starved-refed rats.
Male rats were starved 0-48 hr, and then refed diets containing 0% (F.F.) to 20% corn oil (C.O.) lab chow or 20% coconut oil (C.C.O.) for 1-4 days. Some received phenobarbital sodium (80 mg/kg, i.p. daily) for 1-3 days prior to decapitation. Five cytochrome P-450-dependent indicators were assayed as measures of altered hepatic microsomal function: ethylmorphine N-demethylase (EMDM), N-nitrosodimethylamine (DMN)-N demethylase, aniline hydroxylase (AH), benzo[a]pyrene hydroxylase (AHH) and CO-difference spectra (P-450). Increasing dietary corn oil (0, 0.5, 10, 20%) in control rats resulted in a progressive increase in the activities of these five enzymes. Dietary fat influenced phenobarbital (Pb) inducibility of all mixed-function oxidase (MFO) enzymes measured except AHH. Pb induced the remaining enzymes only 11-22% in animals fed fat-free diet as compared to 119-246% in animals fed coconut oil and corn oil. Rats fed fat-free diet for 21 days without prior food deprivation and administered Pb had 79% more EMDM, 34% more AH and 120% more P-450 than non-induced controls, whereas rats fed 20% corn oil diet had 227% more EMDM, 143% more AH and 128% more P-450. A requirement of dietary fat for induction of MFO by Pb was demonstrated by these starvation-refeeding experiments. Coupled with data recovered from the 21-day studies, these experiments suggest that a compensatory mechanism may be operative during chronic feeding of the fat-free diet to partially return inducibility to the drug-metabolizing system.
D000815:Aniline Hydroxylase / Q000096:biosynthesis; D000818:Animals; D001579:Benzopyrene Hydroxylase / Q000096:biosynthesis; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004041:Dietary Fats / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D005037:Ethylmorphine-N-Demethylase / Q000096:biosynthesis; D007854:Lead / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013217:Starvation
D004041:Dietary Fats; D007854:Lead; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1; D000815:Aniline Hydroxylase; D001579:Benzopyrene Hydroxylase; D010089:Oxidoreductases, N-Demethylating; D005037:Ethylmorphine-N-Demethylase; D010634:Phenobarbital