A role for xanthine oxidase in the loss of cytochrome P-450 evoked by interferon

S. M. Moochhala, K. W. Renton

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

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 languageEnglish
Pages (from-to)944-950
Number of pages7
JournalCanadian Journal of Physiology and Pharmacology
Volume69
Issue number7
DOIs
Publication statusPublished - 1991
Externally publishedYes

ASJC Scopus Subject Areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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