KINETICS OF TRICHLOROACETIC-ACID AND DICHLOROACETIC ACID IN THE ISOLATED-PERFUSED RAT-LIVER

Trichloroacetic acid (TCA) and dichloroacetic acid (DCA) are environme ntal contaminants that are suspected human carcinogens. To obtain more detail on the role of the liver in the kinetics of TCA and DCA, exper imental studies in the isolated perfused rat liver (IPRL) system were conducted. The IPRL system was dosed with either 5 or 50 mu mol of eit her TCA or DCA (25 or 250 mu M initial concentration, respectively), T CA and DCA concentrations were followed in perfusion medium and bile f or 2 h, The chemical concentration in liver was determined at the end of exposure. Liver viability was monitored by measuring leakage of lac tate dehydrogenase (LDH) into perfusion medium and the rate of bile pr oduction. Studies performed with TCA showed that the total TCA concent ration in perfusion medium decreased slightly during the first 30 min of exposure and remained constant thereafter, Most TCA, greater than 9 0% of total, was bound to albumin in the perfusion medium. A low, line ar excretion rate of TCA in bile was obtained. The calculated free TCA concentration in the liver intracellular water space was higher than the unbound TCA concentration in the perfusion medium. Parallel studie s with DCA showed that the DCA concentration in perfusion medium decre ased rapidly. Of the total DCA in the perfusion medium, 60% was bound to albumin. The concentration of DCA in bile decreased over time. Ther e was no DCA detectable in the liver after 2 h of exposure at both DCA concentrations, Enzyme leakage and bile production did not change in the presence of TCA or DCA, indicating that these concentrations were not acutely cytotoxic to the liver, (C) 1998 Academic Press.