Effect of hexachlorophene on hepatic drug-metabolizing enzymes in the rat

Hexachlorophene (HCP) at oral doses of 30-50 mg/kg causes significant increases in hexobarbital sleeping time in Wistar and Sprague-Dawley rats, with the maximum effect occurring 6 hr after administration of the bisphenol. Liver microsomal 0-demethylase activity is simultaneously reduced in rats receiving HCP. Incubation of rat liver microsomes with concentrations of HCP as low as 0.38 nmole/mg of microsomal protein in vitro inhibits the O-demethylase, nitroreductase and phenol UDP-glucuronyl transferase systems and also causes a reduction in the apparent content of cytochromes P-450 and b₅. The concentrations of HCP required to produce a 50 per cent inhibition or reduction in apparent cytochrome contents in vitro range between 4.7 and 98 nmoles HCP/mg of microsomal protein. Some evidence for a common inhibitory mechanism, perhaps involving interaction of HCP with the microsomal membrane, was obtained for the hepatic mixed function oxidase and cytochrome systems.