Uptake of dodecanedioic acid by isolated rat liver

The uptake of dodecanedioic acid (C12), a dicarboxylic acid with 12 carbon atoms, was studied in the isolated perfused rat liver. Fifty pmol of C12 were injected as a bolus into the perfusing liver solution. The concentration of C12 in perfusate samples taken over 2 h from the beginning bf the experiments were analyzed by high performance liquid chromatography. An in vitro experimental session was performed to determine the binding curve of C12 to defatted bovine serum albumin. These data were then used to compute the perfusate C12 free fraction. The number of binding sites on the albumin molecule was equal to 4.29 +/- 0.21 (S.E.), while the affinity constant was 6.33 +/- 0.87 x 10(3) M(-1). Experimental values of perfusate C12 concentration versus time were individually plotted and fitted to a monoexponential decay for each liver perfused. The predicted C12 concentration at time zero averaged 0.354 +/- 0.0375 mu mol/ml. From this value the apparent volume of distribution of C12 was obtained and corresponded to 153.02 +/- 14.56 mi. The disappearance rate constant from the perfusate was 0.0278 +/- 0.0030 min(-1). The C12 half life was 26.6 +/- 2.3 min. The mean hepatic clearance from the perfusate was 4.08 +/- 0.38 ml/min. In conclusion, C12 is quickly taken up by the liver so that in about 100 min it was completely cleared from the perfusate. (C) 1997 Elsevier Science B.V.