N. Ercal et al., IN-VIVO INDEXES OF OXIDATIVE STRESS IN LEAD-EXPOSED C57BL 6 MICE ARE REDUCED BY TREATMENT WITH MESO-2,3-DIMERCAPTOSUCCINIC ACID OR N-ACETYLCYSTEINE/, Free radical biology & medicine, 21(2), 1996, pp. 157-161
Knowledge of lead's capacity to disrupt the prooxidant/antioxidant bal
ance within mammalian tissues suggests that definitive therapy for chr
onic lead poisoning should encompass both chelating and antioxidant ac
tions. The dithiol meso-2,3-Dimercaptosuccinic Acid (DMSA) is the firs
t orally administered metal chelating agent to receive U.S. Food and D
rug Administration (FDA) approval for the treatment of childhood plumb
ism and possesses the potential to function as an antioxidant by remov
ing lead from the site of deleterious oxidation reactions. Five weeks
of lead exposure was found to deplete glutathione (GSH) levels, increa
se oxidized glutathione (GSSG), and promote malondialdehyde (MDA) prod
uction in both liver and brain samples taken from C57BL/6 mice. GSH le
vels increased and GSSG and MDA levels decreased in groups of lead-exp
osed mice that received 1 mmol/kg DMSA or 5.5 mmol/kg N-acetylcysteine
(NAG) for 7 d prior to sacrifice. Treatment with DMSA caused a reduct
ion in blood, liver, and brain lead levels consistent with its functio
n as a chelating agent, while treatment with NAC did not reduce these
lead levels. However, NAC did cause a reduction in indices of oxidativ
e stress in both brain and Liver samples, which implies that this synt
hetic thiol-containing antioxidant is capable of abrogating lead-induc
ed oxidative stress in vivo. Overall, these results suggest that lead-
induced oxidative stress in vivo can be mitigated by pharmacologic int
erventions, which encompass both chelating as well as thiol-mediated a
ntioxidant functions.