Factors influencing the efficiency of chelation therapy

The purpose of the present study was to obtain new data on the effect of age, route, dose and time of metal and chelating agent administration on the efficiency of chelation therapy. The experiments were performed on 1-2 and 6-week-old rats which received radioisotopes of metals--203Pb, 115 mCd, 203Hg and 141Ce intraperitoneally or orally. Chelating agents calcium ethylenediaminetetraacetate (CaEDTA), calcium and zinc diethylenetriaminepentaacetate (CaDTPA, ZnDTPA), 2,3-dimercapto-propane-sulfonate-1 (DMPS), dimercaptosuccinic acid (DMSA) and sodium N-(4-methoxybenzyl)-D-glucamine dithiocarbamate monohydrate (MeOBDCG) were administered twice by intraperitoneal or oral administration as early (immediately and 24 hr after metals) or delayed treatment (24 and 48 or 48 and 72 hr after metals). The animals were killed six days after metal administration and the retention was determined in the whole body, carcass and gut. After intraperitoneal administration of metals and chelating agents chelation therapy had much lower efficacy in younger than older animals. After ingestion of metals oral chelation therapy was more effective in younger than older animals. In suckling rats the treatment effectively reduced metal retention and this was mostly due to decrease in gut retention. This treatment in sucklings was also very effective in condition of late administration. In older rats early oral DMPS treatment after 203Hg ingestion is contraindicated since it increases significantly mercury retention while DMSA and ZnDTPA treatments reduced mercury retention. Delayed oral treatment with ZnDTPA and DMSA caused increased cadmium retention in older rats and decreased retention in sucklings. Opposite to results with CaDTPA, MeOBDCG was effective in reducing cadmium retention also when given as delayed treatment.(ABSTRACT TRUNCATED AT 250 WORDS)