Assessment of rat liver slices as a suitable model system for studying the simultaneous sulphation and glucuronidation of phenolic xenobiotics

Abstract

1. In most mammals, the xenobiotic 1-naphthol undergoes conjugation to produce predominantly the sulphate and glucuronide metabolites. 2. Using 1-naphthol, we established and validated rat liver slices as a model system to assess simultaneously the relative contributions of sulphation and glucuronidation to the metabolism of simple phenolic xenobiotics. 3. Determination of kinetic parameters for 1-naphthol sulphation showed identical affinity (Km 5 mu M) in rat liver slices and in rat liver cytosol. 4. In liver slices, at low substrate concentrations (10 mu M 1-naphthol), sulphation was the predominant pathway but was readily saturated, whereas at high concentrations of 1- naphthol (100 mu M) glucuronidation predominated. 5. In subcellular fractions, the Km for sulphation of 1-naphthol (5 mu M) by liver cytosol was substantially lower than the Km for glucuronidation of 1-naphthol (48 mu M) in liver microsomes, indicating saturation of sulphation by acceptor substrate was principally responsible for the shift towards glucuronidation at higher concentrations of 1-naphthol.