Abstract
It has been suggested that the loss of cytochrome P-450, which is mediated by interferon and its inducers, can result from the generation of free radical species by the enzyme xanthine oxidase. Cytochrome P-450, aminopyrine N-demethylase, and ethoxyresorufin deethylase were depressed by 35, 36, and 38%, respectively, in the livers of hamsters 24 h following the administration of a synthetic interferon (IFN-α-Con1) which contains the most frequent amino acid sequences of the human subtypes. Interferon increased the activities of the D and O forms of xanthine oxidase by 65 and 74%, respectively, in the same animals. The induction of the D form of xanthine oxidase, which is the precursor of the O form, preceded the loss in cytochrome P-450. The protein synthesis inhibitor, actinomycin D, prevented the interferon-induced loss of drug biotransformation and the increase in xanthine oxidase. The free radical scavenger, α-tocopherol, and the xanthine oxidase inhibitor, allopurinol, also prevented the loss of cytochrome P-450 mediated by the interferon inducer poly rI.rC. In chickens in which xanthine oxidase cannot be formed, poly rI.rC had no effect on cytochrome P-450 levels. These results suggest that xanthine oxidase induction may play some role in the interferon-mediated loss of cytochrome P-450.
Original language | English |
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Pages (from-to) | 944-950 |
Number of pages | 7 |
Journal | Canadian Journal of Physiology and Pharmacology |
Volume | 69 |
Issue number | 7 |
DOIs | |
Publication status | Published - 1991 |
Externally published | Yes |
ASJC Scopus Subject Areas
- Physiology
- Pharmacology
- Physiology (medical)
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't