Abstract
Summary
1. Many acute irritants, e.g., turpentine, mimicked Freund's adjuvant (FA) in causing rapid depression of hexobarbital and cyclophosphamide metabolism in rats in vivo.
2. Metabolism of cyclophosphamide and aminopyrine in vitro by liver homogenates was often subnormal if liver donor animals had been acutely inflamed (rear paw, tail) 48 hr previously.
3. Three classes of irritants/inflammagenic stimuli were distinguished by their effects on liver drug metabolism.
4. Carrageenan as routinely used for anti-inflammatory screening had a peculiar, selective effect on drug metabolism.
5. Drug metabolism was distinctly subnormal in animals inoculated with FA (rear paw, tail) at all stages prior to developing arthritis.
6. Drug metabolism was almost normal in prearthritic animals when FA was inoculated ip in a front paw or ear. Ear inoculations induced arthritis consistently in Lewis and Wistar rats.
7. Several drugs which prevented development of arthritis failed to normalize drug metabolism in the 4-day period after inoculating FA in rear paw or tail.
8. 6-MP and dexamethasone prevented the acute depression of drug metabolism and may be prototypes of a new class of anti-injury agents.
We are grateful to Dr. C. M. Pearson for continued encouragement, the USPHS (NIH Grant GM 15759) for financial support and to Mrs. D. J. Whitehouse for surgical assistance.
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