Mathematical model for cadmium kinetics in the isolated perfused rat liver system

The isolated perfused rat liver (IPRL) preparation has previously been used to investigate cadmium kinetics. A mathematical model which has been developed to simulate cadmium kinetics in the IPRL is described. The model takes into consideration binding of cadmium to both intra- and extracellular proteins and the mechanisms of membrane transport. In addition, the competitive interaction of cadmium with endogenous zinc is incorporated into the model. Model simulations of the behavior of cadmium and zinc in the perfusion medium, liver, and bile are compared to results from IPRL experiments involving cadmium doses ranging from 0.29 to 15.6 mumol. A major contribution of this model is the identification, from a kinetic point of view, of two high-molecular-weight classes of intracellular cadmium-binding species which can be identified by two distinct peaks in Sephadex G-75 profiles of hepatic cytosol. This model can be utilized for the quantitation of kinetics based on specific mechanisms involved in cadmium hepatic kinetics.