PuSH - Publikationsserver des Helmholtz Zentrums München

Saghir, S.A.* ; Fried, K.* ; Rozman, K.K.

Kinetics of monochloroacetic acid in adult male rats after intravenous injection of a subtoxic and a toxic dose.

J. Pharmacol. Exp. Ther. 296, 617-627 (2001)
Verlagsversion Volltext PMC
Free by publisher
Distribution, metabolism, and excretion of monochloroacetic acid (MCA) were examined in adult male rats at a subtoxic (10 mg/kg) and a toxic (75 mg/kg) dose. Rats were injected i.v. with [14C]MCA and housed individually. Urine and feces were collected. Animals were euthanized at different time intervals after dosing and tissues procured. Radioactivity in aliquots showed very rapid distribution of MCA to tissues. Concentrations of MCA in plasma, liver, heart, lungs, and brown fat paralleled each other, whereas those in brain and thymus did not. There was no dose proportionality in tissue concentrations. Elimination of MCA from plasma required modeling by two compartments. Most of the radioactivity found in plasma was parent MCA. Elimination rate constant (K(10)) and distribution rate constant (K(12)) were greatly reduced at the toxic dose. Elimination of the toxic dose was further retarded due to increased retention of MCA in the peripheral compartment as indicated by increased mean residence times in most tissues. A very large fraction of dose was found in the gastrointestinal tract, almost all of which was reabsorbed. Attempts to reduce toxicity by blocking the enterohepatic circulation with activated charcoal or cholestyramine failed. Radioactivity found in bile was associated with one metabolite more polar than the parent compound. A very large fraction of dose (73 and 59%) was found in urine, 55 to 68% of which was parent MCA. The rate-determining step in the toxicity of MCA was identified as its detoxification by the liver. A therapeutic approach in MCA intoxications is suggested.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter MCA monochloroacetic acid TCA tricarboxylic acid GI gastrointestinal HPLC high performance liquid chromatography AUC area under the curve MRT mean residence time; DRINKING-WATER; PRODUCTS
ISSN (print) / ISBN 0022-3565
e-ISSN 1521-0103
Zeitschrift Journal of Pharmacology and Experimental Therapeutics
Quellenangaben Band: 296, Heft: 2, Seiten: 617-627 Artikelnummer: , Supplement: ,
Verlag American Society for Pharmacology and Experimental Therapeutics (ASPET)
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Toxicology and Pharmacology (TOXI)