Effects of betamethasone on the in vitro and in vivo 2-hydroxylation of biphenyl in the rat

Abstract

The in vitro addition of betamethasone to rat liver microsomes caused a concentration-dependent stimulation of biphenyl 2-hydroxylation. At a 100 microM concentration of betamethasone, the formation of 2-hydroxybiphenyl was increased by approximately 4-fold in microsomes from 28-day-old rats and 10-fold in liver microsomes from 5-day-old rats. The steroid had little or no effect on the hydroxylation of biphenyl in the 3- or 4-position except at the highest concentration tested (1 mM), where a 20-30% inhibition was observed. The ip injection of 0.01 to 10 mumol of betamethasone to 5-day-old rats had little or no effect on the total body metabolism of 0.01 to 3.5 mumol of biphenyl-2-3H to 2-hydroxybiphenyl as measured by 3H2O formation. Although betamethasone had no effect on the 2-hydroxylation of biphenyl in the intact rat, this reaction was stimulated 4- to 9-fold by the addition of 100 microM betamethasone to hepatocyte monolayer cultures.