Effect of a Perfluorochemical Emulsion on the Rat Hepatic Mixed Function Oxidase System

Abstract

The perfluorochemical components of synthetic oxygen transporting emulsions may persist in hepatic tissue. After a single 30% blood exchange with the perfluorochemical emulsion, Fluosol-DA 20%, the effects on the microsomal metabolism of 7-methoxycoumarin and 7-ethoxycoumarin were studied over a 9-week period. Fluosol-DA treated animals were compared with controls (sham) and hetastarch-treated controls. Changes in dealkylase activities were compared with induction by phenobarbitone and 3-methylcholanthrene. The liver to body weight ratio increased by 49% in Fluosol-DA-treated rats over the controls at 1 week and the microsomal protein was increased in the Fluosol-DA-treated rats after 4 and 9 weeks. Fluosol-DA treatment induced 7-methoxycoumarin demethylase with peak differences occurring at 1 week and a Vmax 75% greater than controls. Fluosol-DA was a more potent inducer of demethylase than phenobarbitone. In addition, 7-ethoxycoumarin de-ethylase was induced by Fluosol-DA with a peak induction at 4 weeks. The Vmax at 4 weeks in Fluosol-DA-treated rats was 122% greater than control. In this case, Fluosol-DA produced less induction in de-ethylase than 3-methylcholanthrene. These studies show that Fluosol-DA induces more than one form of cytochrome P450 and the effects resemble those of phenobarbitone more than those of 3-methylcholanthrene. Hetastarch, a plasma expander, did not affect liver weights, microsomal protein content, or the cytochrome P450 system.