Coordinate Modulation of Murine Hepatic Xanthine Oxidase Activity and the Cytochrome P-450 System by Interferons

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Abstract
The role of xanthine oxidase (XO) in the interferon (IFN)-dependent modulation of the hepatic cytochrome P-450 system was assessed in SENCAR mice. Intraperitoneal administration of 104–105 units of IFN-γ resulted in dose-dependent increases in hepatic XO activities. XO activity was significantly elevated within 12 h of IFN-γ treatment, and reached a maximum between 24–48 h, and returned to basal levels within 72–96 h. Although the kinetics of increase and decline of XO activity correlated with the loss and subsequent recovery of hepatic P-450 levels, there was no quantitative correlation between hapatic XO activity and P-450 content. Comparable results were obtained in mice pretreated with the P-450 inducer Aroclor 1254 3 days prior to IFN-γ administration. The increases in XO activity following IFN-γ treatment were the consequence of increases in xanthine dehydrogenase (XD), and the conversion of XD to XO. The ad libitum administration of allopurinol to IFN-γ-treated mice reduced XO specific activity to ∼4% of the basal activity of control mice, but did not prevent reductions in cytochrome P-450 levels or the activities of two P-450 dependent monooxygenases. Collectively, these data suggest that the reductions in the hepatic P-450 system noted after IFN administration are not a consequence of elevated XO activities.

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