Comparative effects of repeated parenteral administration of several chelators on the distribution and excretion of cobalt.
Effects of repeated ip administration of glutathione, N-acetyl-L-cysteine (NAC), 2,3-dimercaptosuccinic acid (DMSA), ethylendiamine-tetraacetic acid (EDTA), and diethylentriamepentaacetic acid (DTPA) on the distribution and excretion of cobalt were assessed in Sprague-Dawley rats. Groups of ten animals received intraperitoneally 0.06 mmol CoCl2/kg/day, three days/week for four weeks. 24 hr after the last injection, daily chelation therapy was initiated. Rats received one of the chelators or saline for 5 days. The animals were housed in metabolic cages and urine and feces were collected daily for 5 days after which time the rats were killed and the concentration of cobalt was determined in various tissues. Glutathione, NAC and DTPA significantly increased the excretion of cobalt into urine whereas EDTA, NAC and DMSA were the most effective chelators increasing the fecal elimination of cobalt. The concentration of cobalt in the various tissues was only decreased by NAC (liver and spleen) and glutathione (spleen). The observed increase in the cobalt excretion with certain chelators would suggest that increasing the duration of chelation therapy may decrease the concentrations of cobalt in tissues and hence, reduce the toxicity of the metal.
Llobet
J M
JM
Laboratory of Toxicology and Biochemistry, Faculty of Medicine, University of Barcelona, Spain.
Domingo
J L
JL
Corbella
J
J
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology*; D003035:Cobalt / Q000493:pharmacokinetics* / Q000652:urine; D004492:Edetic Acid / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D004369:Pentetic Acid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D004113:Succimer / Q000494:pharmacology
D002614:Chelating Agents; D003035:Cobalt; D004369:Pentetic Acid; D004492:Edetic Acid; D004113:Succimer; C018021:cobaltous chloride; D005978:Glutathione; D000111:Acetylcysteine