Zl. Gong et Hl. Evans, EFFECT OF CHELATION WITH MESO-DIMERCAPTOSUCCINIC ACID (DMSA) BEFORE AND AFTER THE APPEARANCE OF LEAD-INDUCED NEUROTOXICITY IN THE RAT, Toxicology and applied pharmacology, 144(2), 1997, pp. 205-214
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.