Kinetics of trichloroacetic acid and dichloroacetic acid in the isolated perfused rat liver.
Trichloroacetic acid (TCA) and dichloroacetic acid (DCA) are environmental contaminants that are suspected human carcinogens. To obtain more detail on the role of the liver in the kinetics of TCA and DCA, experimental studies in the isolated perfused rat liver (IPRL) system were conducted. The IPRL system was dosed with either 5 or 50 micromol of either TCA or DCA (25 or 250 microM initial concentration, respectively). TCA and DCA concentrations were followed in perfusion medium and bile for 2 h. The chemical concentration in liver was determined at the end of exposure. Liver viability was monitored by measuring leakage of lactate dehydrogenase (LDH) into perfusion medium and the rate of bile production. Studies performed with TCA showed that the total TCA concentration in perfusion medium decreased slightly during the first 30 min of exposure and remained constant thereafter. Most TCA, greater than 90% of total, was bound to albumin in the perfusion medium. A low, linear 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 studies with DCA showed that the DCA concentration in perfusion medium decreased rapidly. Of the total DCA in the perfusion medium, 60% was bound to albumin. The concentration of DCA in bile decreased over time. There 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.
Toxopeus
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Department of Pharmacology and Toxicology, Wright State University, Dayton, Ohio 45435, USA.
Frazier
J M
JM
D000818:Animals; D001646:Bile / Q000737:chemistry; D001826:Body Fluids / Q000737:chemistry; D003999:Dichloroacetic Acid / Q000032:analysis / Q000493:pharmacokinetics*; D004785:Environmental Pollutants / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D011916:Rats, Inbred F344; D014238:Trichloroacetic Acid / Q000032:analysis / Q000493:pharmacokinetics*
D004785:Environmental Pollutants; D014238:Trichloroacetic Acid; D003999:Dichloroacetic Acid; D007770:L-Lactate Dehydrogenase