The effect of chelating agents on the excretion of endogenous metals

Abstract

The effect of various chelating agents on the urinary elimination of several endogenous metals was determined in male Swiss Webster mice. The chelating agents diethylenetriaminepentaacetic acid (DTPA), ethylenediaminetetraacetic acid (EDTA), 2,3-dimercaptosuccinic acid (DMSA), penicillamine (PEN), sodium diethyldithiocarbamate (DDC), nitrilotriacetic acid (NTA), and 2,3-dimercaptopropanol (BAL) were administered once daily for 3 consecutive days or twice daily for 7 consecutive days at a dose equivalent to one-fourth of their respective LD50 values. Neither treatment protocol produced significant pathological lesions visible by light microscopic examination of heart, liver, skeletal muscle, small intestine, and kidney. However, marked weight losses were observed in mice given EDTA or DTPA twice daily for 7 days. The concentrations of Zn, Cu, Mg, Mn, Fe, and Ca were determined in daily urine from mice given chelators once daily for 3 consecutive days. DTPA significantly increased the urinary elimination of Cu, Fe, Zn, and Mn. The urinary excretion of Fe, Zn, and Mn was increased by EDTA. Treatment with DMSA or BAL increased the urinary elimination of Fe. Administration of NTA had no effect on the urinary elimination of any of the metals studied. None of the chelators significantly affected the excretion of Mg or Ca. Thus, certain chelating agents were shown to produce marked effects on the excretion of endogenous metals which suggests that chronic therapy with these agents may be accompanied by possible depletion of essential metals.