J. Anim Sci.
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J. Anim Sci. 1983. 56:887-894.
© 1983 American Society of Animal Science
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Effect of Phenobarbital on Toxicity of Pyrrolizidine (Senecio) Alkaloids in Sheep1

R. A. Swick2,3,, C. L. Miranda4, P. R. Cheeke2,5 and D. R. Buhler4

Oregon State University, Corvallis 97331

5 To whom reprint requests should be sent.

Abstract

The effect of prolonged phenobarbital (PB) administration on the toxicity of Senecio jacobaea (SJ) was studied in sheep. Hepatic microsomal mixed function oxidase (MFO) activity was monitored. Pentobarbital sleeping times were decreased after 17 d of treatment, indicating initial induction of MFO. At 105 d of treatment, hepatic microsomal aminopyrine N-demethylase activity and cytochrome P-450 levels were increased (P<.05) as a result of PB administration. No differences (P>.05) were observed in activity of microsomal epoxide hydrolase, glutathione S-transferase or liver glutathione as a result of SJ and(or) PB. Epoxide hydrolase activity in control sheep was about fivefold higher than values previously reported for rats. Liver Cu concentration was increased (P<.05) in sheep receiving PB and SJ when compared with controls, but no differences (P>.05) were observed in the hepatic intracellular distribution of Cu as a result of PB and(or) SJ. Histopathological examination of liver revealed greater incidence and severity of lesions in animals receiving SJ, but PB did not appear to potentiate SJ intoxication. The results suggest that MFO induction by PB does not increase the susceptibility of sheep to SJ intoxication. Sheep possess a high activity of hepatic microsomal epoxide hydrolase which could account for their resistance to SJ intoxication.

Footnotes

1 Technical Paper No. 6168, Oregon Agr. Exp. Sta.

2 Dept. of Anim. Sci.

3 Present address: Monsanto Chemical Co., St. Louis, MO.

4 Dept. of Agr. Chem.






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