Perfusion analysis of periportal and centrilobular metabolism of paraoxon in the rat liver

Paraoxon infused into the rat liver during perfusion in situ with Waymouth's medium underwent chromatographic translobular migration with an apparent hepatic transit time of 3 min. Intralobular heterogeneity of paraoxon metabolism was examined by analyzing metabolites produced under conditions minimizing the chromatographic translobular migration of paraoxon. Periportal and centrilobular activities were estimated following forward and retrograde infusion of paraoxon, respectively. Centrilobular hepatocytes exhibited nearly twice the metabolic rate of the periportal cells. Pretreatment of the rat with DDE resulted in about a threefold increase in the ratio of oxidative deethylation to hydrolytic dearylation in the centrilobular region. The differentials observed by these analyses were less pronounced than expected from enzyme analyses in vitro, possibly reflecting secondary metabolism or intracellular heterogeneity of metabolic activities.