ISOZYME SELECTIVITY OF THE INHIBITION OF RAT-LIVER CYTOCHROMES P-450 BY CHLORAMPHENICOL INVIVO

  • 1 January 1985
    • journal article
    • research article
    • Vol. 28  (3) , 290-296
Abstract
The isozyme-selectivity of chloramphenicol as an inhibitor of rat liver cytochromes P-450 has been investigated. Untreated rats and rats treated with the inducers phenobarbital, .beta.-naphthoflavone, pregnenolone 16.alpha.-carbonitrile, and clofibrate have been injected intraperitoneally with chloramphenicol, and inhibition of specific cytochrome P-450 isozymes had been assessed by monitoring the metabolism of warfarin, testosterone, isosafrole, or lauric acid in subsequently prepared hepatic microsomal preparations. Of eight major cytochrome P-450 isozymes which could be monitored in this fashion, three were inhibited by more than 50% by a dose of chloramphenicol of 300 mg/kg, whereas no evidence of inhibition of the remaining isozymes was obtained. P-450PB-C, an isozyme which is present in significant amounts in untreated rats and which is induced approximately 2-fold by phenobarbital, was the most susceptible cytochrome P-450 to inhibition by chloramphenicol both in vivo and in vitro. P-450PB-B, the major phenobarbital-inducible isozyme, and P-450UT-A, a male-specific testosterone 2.alpha.- and 16.alpha.-hydroxylase, were intermediate in their susceptibility to chloramphenicol. In contrast, the major isozymes induced by .beta.-naphthoflavone, pregnenolone 16.alpha.-carbonitrile, and clofibrate, as well as a constitutive testosterone 7.alpha.-hydroxylase, were not inhibited by chloramphenicol.