EFFECT OF CHELATING-AGENTS ON THE EXCRETION OF COPPER, ZINC AND IRON IN THE BILE AND URINE OF SHEEP

The effect of tetrathiomolybdate (TM), disodium calcium ethylenediamin e tetraacetate (EDTA), D-penicillamine (PEN), 2-3 dimercapto-1-propano l (BAL) and dimethyl dithiocarbamate (DDC) administration on biliary a nd urinary excretion of copper (Cu), zinc (Zn) and iron (Fe) was inves tigated in sheep on a low Cu diet (Group A) and a high Cu diet (Group B). Only biliary Cu excretion increased significantly (P<0.01) with TM treatment. Urinary; Cu excretion increased (P<0.01) following PEN tre atment. TM, EDTA, PEN, BU and DDC adminstration increased Cu excretion via bile and urine by 254, 11, 266, 46 and 16%, respectively in Group A sheep, and by 354, 13, 196, 20 and (-) 31% in Group B sheep. Urinar y Zn excretion increased (P<0.01) following EDTA and PEN treatments. O nly urinary Fe excretion increased (P<0.01) with EDTA treatment. The r esults show that TM and PEN are the most efficient decoppering agents, but PEN unlike TM also removes Zn. The major routes of excretion of C u chelates by TM and PEN are different. TM increases Cu excretion sign ificantly (P<0.05 in Group A and P<0.01 in Group B) in bile with only a slight increase in urinary Cu whereas PEN increases Cu excretion sig nificantly (P<0.01) in urine. Therefore from a therapeutic view, a com bination therapy of TM and PEN would be useful to maximize Cu removal from the body.