Indexed on: 16 Jun '09Published on: 16 Jun '09Published in: Journal of Biochemical and Molecular Toxicology
The effects of zymosan on transport, distribution, and metabolism of octanoate in the perfused rat liver were investigated using the multiple-indicator dilution technique. Livers were perfused with 300 microM octanoate in the absence or in the presence of 100 microg/mL zymosan. Tracer amounts of [1-14C]octanoate, [3H] water, and [131I]albumin were injected into the portal vein, and the effluent perfusate was fractionated. The normalized dilution curves were analyzed by means of a space-distributed variable transit time model. Zymosan decreased the space into which octanoate undergoes flow-limited distribution, possibly the first cellular exchanging pool represented by plasma membranes and their adjacencies. However, the rate of transfer of octanoate from the plasma membrane into the rest of the cell was not modified as indicated by the similar values of the influx rates and also the net uptake of octanoate per unit of accessible cellular volume. However, when referred to the wet weight of the liver, the net uptake of octanoate was 37.5% reduced, a value corresponding to the diminution of the cellular accessible space. It can be concluded that an exclusion of a fraction of the liver parenchyma from the microcirculation is the main mechanism by which zymosan reduces the metabolism of exogenous octanoate.