Abstract
Hydroxylation of niflumic acid to 4'-hydroxyniflumic acid and 5-hydroxyniflumic acid by rat liver microsomes from untreated animals or phenobarbital-pretreated animals has been demonstrated. Pretreatment of rats with phenobarbital (50 mg/kg) increased the 4'-hydroxylase activity 53%, whereas the 5-hydroxylase activity was increased 205%. Niflumic acid inhibited both the 4'- and 5-hydroxylases at concentrations greater than 1 mM. Competitive inhibition of 4'- or 5-hydroxylase was observed with SKF 525-A. WIN 13099 inhibited both hydroxylases noncompetitively. With freshly prepared microsomes, acetone, at concentrations up to 10% (v/v), enhanced 4'-hydroxylase markedly but had little effect on 5-hydroxylase. With frozen and aged microsomes, maximum enhancement of 4'-hydroxylase was obtained at 5% acetone: little or no effect on 5-hydroxylase was observed at the same concentration. At 10% acetone, the 4'- and 5-hydroxylases were inhibited 33 and 73%, respectively. The data indicate that at least two different enzyme systems are involved in the hydroxylation of niflumic acid by the microsomes of rat liver.
Footnotes
- Received September 6, 1974.
- Copyright © 1975 by The American Society for Pharmacology and Experimental Therapeutics
DMD articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|