Effect of phenobarbital pretreatment on benzene biotransformation in the rat. II. 9,000 g supernatant and isolated perfused liver versus living rat.

Abstract

Factors responsible for different quantitative effect of phenobarbital (PB) pretreatment (sodium phenobarbital, 50 mg kg-1 day-1 for 3 days) on benzene metabolism to phenol in vivo and in vitro were studied in male Wistar rats. A more than 4-fold increase of benzene metabolism was observed wih 9,000 g supernatant of liver homogenate, 2.8- to 4-fold increase with isolated perfused liver; phenol formation in vivo after oral benzene was increased by PB 2-fold, but only shortly following benzene administration and the enhancement rapidly diminished to 1.15-fold increase in the total excreted phenol. Benzene concentrations i 9,000 g supernatant incubations were 2 mM, those with isolated perfused livers were up to 4 mM, but those in blood in vivo were below 0.3 mM; the effect of PB induction in vivo disappeared along with decreasing benzene and increasing phenol blood concentrations which surpassed benzene 2-3 h after oral benzene administration. The effect of benzene concentration on the manifestation of PB induction is also supported by almost a 2-fold increased phenol formation in PB rats over controls in vivo after repeated administration of benzene. The elimination of radioactive metabolites of orally administered benzene-14C, 3 mmoles kg-1, in urine was markedly inhibited by intraperitoneal administration of phenol (1.2 mmol kg-1), but not by pyrocatechol, resorcinol or hydroquinol (0.6 mmole kg-1, respectively) suggesting that phenol might inhibit benzene metabolism in vivo especially when its concentration exceeds that of benzene.