The influence of dose of phenobarbital and interval to measurement on concentration of liver enzymes in barrows and gilts.
The administration of xenobiotics such as phenobarbital (PB) and chlorinated hydrocarbons to rats, mice and several other species has been shown to increase the level of hepatic mixed function oxidases. Experiments were conducted to establish the effect of dose of PB, sex of animals, and effect of interval from dose to measurement on concentration of hepatic enzymes in barrows and gilts 6 to 9 mo of age and weighing 100 to 120 kg. Animals given 1 or 2 g PB for 3 d had higher concentrations of microsomal protein cytochrome b5 and P-450 and NADPH cytochrome c reductase than control animals (P less than .01). Animals given 2 g PB had 3.5 times as much cytochrome P 450 as did controls. Barrows and gilts did not differ from each other in any variables measured (P less than .20). In a study of the time course of induction all animals given PB had higher levels of microsomal protein, cytochrome P-450 and reductase in 24 h than controls; however, cytochrome b5 was depressed on d 1 and was elevated by d 3. Concentration of cytochrome P-450 reached a maximum by d 7 (P less than .01); cytochromes b5 and c reductase reached a maximum by d 9 and 3, respectively (P less than .01). Levels of cytochrome P-450 were higher in gilts than in barrows on all days following PB treatment (P less than .04). Microsomal protein, cytochrome b5, cytochrome P-450 and reductase remained elevated for 6 d after the last treatment with PB.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003573:Cytochrome b Group / Q000378:metabolism; D015786:Cytochromes b5; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D008099:Liver / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology*; D012737:Sex Factors; D013552:Swine / Q000378:metabolism*; D013997:Time Factors
D003573:Cytochrome b Group; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D009251:NADPH-Ferrihemoprotein Reductase; D010634:Phenobarbital