Chelation in metal intoxication: XIV. Comparative effect of thiol and amino chelators on lead-poisoned rats with normal or damaged kidneys

Abstract

d-Penicillamine (DPA), diethyl-dithiocarbamate (DDC), l-cysteine, ethylenediaminetetraacetic acid (EDTA), cyclohex-ylenediaminetetraacetic acid (CDTA), and diethylene triamine pentaacetic acid (DTPA) were compared for their efficacy to enhance urinary excretin of Pb, to reduce Pb concentration of body organs, and to restore the enhanced urinary excretion of δ-aminolevulinic acid (δ-ALA), the inhibited activities of blood δ-ALA dehydratase, and renal enzymes in Pb-administered rats (10 mg/kg, po, 4 weeks) with normal or experimentally damaged kidneys. The acute renal damage was induced by uranyl acetate (3 mg/kg, sc, once) prior to treatment with the chelators (0.3 mmol/kg, ip, twice) and evaluated by enhanced urinary excretion of diagnostic enzymes and inhibition in their renal activities. Among thiol chelators, DPA was the most effective followed by DDC in enhancing the urinary excretion of Pb, reducing the concentration of Pb in blood, kidneys and liver, and in restoring Pb-induced biological alterations in urine, blood, and kidneys. Among amino carboxylic acids, DTPA was the most effective and EDTA and CDTA were about equally potent in countering Pb toxicity. Protection was more marked in animals with normal kidneys than in those with acutely damaged kidneys.