IRON TISSUE AND EXCRETA CHANGES INDUCED BY ETHYLENEDIAMINE-N,N'-BIS(2-HYDROXYPHENYLACETIC ACID) IN DOGS

  • 1 January 1980
    • journal article
    • research article
    • Vol. 95  (5) , 771-776
Abstract
The use of EDBPHA [ethylenediamine-N,N''-bis(2-hydroxyphenylacetic acid)] as a potential Fe chelator in cases of hemochromatosis provided impetus for investigating its toxicology. Because a reddish coloration of excreta was observed during subchronic administration of the drug to dogs, measurements of Fe concentrations in blood, excreta and hematopoietic tissues were made. Groups of beagle dogs of both sexes were injected i.v. with EDBPHA doses of 6, 12 or 18 mg/kg or were given capsules containing doses of 30, 100 or 240 mg/kg for 14 days. Control dogs received either saline i.v. or empty gelatin capsules orally. In addition to the monitoring of toxicological effects, Fe levels in plasma, urine, feces, liver, spleen and kidney were monitored before drug, at the end of treatment, and after a 16 day recovery period. In the absence of Hb and hematocrit changes, i.v. EDBPHA reduced renal Fe 40% and hepatic Fe 15 to 25% without altering splenic Fe. Serum Fe rose 34 to 54%, urinary Fe 80 to 119%, and fecal Fe 23 to 41%. Oral EDBPHA did not induce changes in tissue Fe or excreta Fe, but serum Fe was increased 22 to 29%. These alterations in Fe concentrations were transient and may be related to Fe redistribution and inactivation of drug by liver.