Restoration of impaired drug metabolism of rats with adjuvant induced disease by two steroids with different influence on drug biotransformation.

Adjuvant Induced Disease (AID) produced by intradermal administration of Freund's Adjuvant to Fisher female rats, caused inflammation and severe impairment of the drug metabolic activity of the liver. Treatment with pregnenolone-16 alpha-carbonitrile (1), or triamcinolone (2) caused a mild and a great reduction of the produced arthritis, respectively, while these steroids completely restored the established drug metabolic impairment of the AID rats. It is concluded that: (i) There is a cross-linkage between arthritis and liver function, the effect of the former to the latter is greater than vice versa. (ii) The action of 1 on the impaired hepatic drug metabolic activity is direct, while that of 2 is indirect. (iii) The effect of the two steroids on AID and liver drug metabolism is not mediated via a protective action on lipid peroxidation.