EFFECT OF CHELATION WITH MESO-DIMERCAPTOSUCCINIC ACID (DMSA) BEFORE AND AFTER THE APPEARANCE OF LEAD-INDUCED NEUROTOXICITY IN THE RAT

This paper examines whether a chelating agent (DMSA) can prevent and r everse the effects of lead (Pb) as evidenced by changes in brain glial fibrillary acidic protein (GEAR) concentration and in the habituation pattern of rearing behavior. Male F344 rats (42 days old) received Pb acetate at 150 or 2000 ppm as ph in their drinking water for 21 days and returned to regular water for another 21 days to observe recovery. Blood Pb (BPb) concentration rose to 37 and 82 mu g/dl for 150 and 20 00 ppm, respectively. Rats exposed to 150 ppm Pb exhibited changes in GFAP concentration and behavioral hyperactivity, when placed in an unf amiliar cage. The 2000 ppm Pb exposure caused greater changes in GFAP, but behavioral hyperactivity appeared only postexposure, when BPb was declining. Chelation (DMSA, 50 mg/kg po, 3 times/week for 21 days) de creased the BPb concentration, and prevented and reversed the Pb-induc ed changes in GFAP and rearing, but not in body weight. Administration of DMSA by itself for 21 days caused no untoward effects in brain GFA P, behavior, or body weight. Concurrent administration of DMSA and Pb resulted in no evidence of additive toxicity. Results indicate that: ( 1) A brief behavioral test of habituation is a sensitive index of neur otoxicity and chelating therapy; (2) Pb-induced hyperactivity depends upon BPb concentration regardless of whether activity is measured duri ng or after exposure; (3) repeated treatment with DMSA is effective in reducing Pb neurotoxicity; (4) there was no evidence that DMSA enhanc ed the absorption of Pb. The finding that DMSA administered late in ex posure can hasten the recovery of toxic signs suggests that extracellu lar Pb continues to play a significant role even after toxic signs hav e appeared. (C) 1997 Academic Press.