title: Combined chelation therapy in reducing tissue lead concentrations in suckling rats.
abstract: The very young are more prone to lead poisoning than adults, and the treatment with chelating agents, either as monotherapy or combined treatment, is still a matter of dispute. The purpose of this work was to evaluate the efficiency of three chelating agents administered either as monotherapies or as combined treatments in sucklings. Lead acetate (5 mg Pb kg(-1) i.p.) was administered to the 7-day-old rat pups in eight litters on experimental day 1 and chelating agents on experimental days 2 and 3. Pups were divided into six groups: (1) untreated control; (2) EDTA (calcium disodium ethylendiaminetetraacetate, 0.3 mmol kg(-1) i.p. at 4 p.m.); (3) meso-DMSA (meso-2,3-dimeracaptosuccinic acid, 0.5 mmol kg(-1) p.o. at 10 a.m.); (4) rac-DMSA (racemic-2,3-dimeracaptosuccinic acid, 0.5 mmol kg(-1) p.o. at 10 a.m.); (5) EDTA+meso-DMSA; and (6) EDTA+rac-DMSA. Rats were killed on experimental day 5. Tissue element concentrations were analyzed by atomic absorption spectrometry. Treatment with EDTA did not affect tissue Pb, but it reduced Zn in the carcass and liver. Meso-DMSA reduced Pb in the kidneys and brain, and it did not affect organ essential elements. Rac-DMSA most efficiently reduced Pb concentrations in the carcass, kidneys and brain, but it also reduced Zn and Cu in the liver and Zn in the kidneys. Combined treatments with EDTA never improved the efficiency of either DMSA isoform in decreasing tissue Pb but they did reduce tissue Zn concentrations. All treatments caused the same decrease in the carcass Ca concentrations. The results do not support combined treatment in this age group, which is especially sensitive to trace element deficiencies, and suggest that meso-DMSA might be the treatment of choice in acute lead poisoning in infants.
authors.affiliation: Mineral Metabolism Unit, Institute for Medical Research and Occupational Health, Zagreb, Republic of Croatia.
authors.forename: K
authors.initials: K
authors.lastname: Kostial
authors.forename: M
authors.initials: M
authors.lastname: Blanusa
authors.forename: M
authors.initials: M
authors.lastname: Piasek
authors.forename: N
authors.initials: N
authors.lastname: Restek-Samarzija
authors.forename: M M
authors.initials: MM
authors.lastname: Jones
authors.forename: P K
authors.initials: PK
authors.lastname: Singh
mesh_terms: D000818:Animals; D000833:Animals, Suckling; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004492:Edetic Acid / Q000627:therapeutic use*; D005260:Female; D007501:Iron / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007854:Lead / Q000378:metabolism* / Q000633:toxicity; D007855:Lead Poisoning / Q000378:metabolism / Q000517:prevention & control*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D004113:Succimer / Q000737:chemistry / Q000627:therapeutic use*; D015032:Zinc / Q000378:metabolism
chemical_list: D002614:Chelating Agents; D007854:Lead; D004492:Edetic Acid; D004113:Succimer; D007501:Iron; D015032:Zinc; D002118:Calcium