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The Influence of Dose of Phenobarbital and Interval to Measurement on Concentration of Liver Enzymes in Barrows and Gilts

University of Illinois², Urbana 61801

Abstract

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<.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<.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<.01); cytochromes b⁵ and c reductase reached a maximum by d 9 and 3, respectively (P<.01). Levels of cytochrome P-450 were higher in gilts than in barrows on all days following PB treatment (P<.04). Microsomal protein, cytochrome b⁵, cytochrome P-450 and reductase remained elevated for 6 d after the last treatment with PB. Animals given PB had increased concentrations of enzymes within 1 d after the beginning of treatment and concentrations remained above base line at least 6 d following the last treatment. Although barrows and gilts responded similarly to 1 or 2 g PB given for three consecutive days, their response over the following 6 d differed significantly.

¹ Current address: Div. of Reprod. Toxicol. and Pharmacol., Dept. of Obstet. and Gynecol., Univ. of Arkansas Med. School, 4301 West Markham Street, Slot 518, Little Rock, AR 72205.

² Dept. of Anim. Sci., 1301 Taft Drive, Urbana, IL 61801.

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