PMID- 8818630
OWN - NLM
STAT- MEDLINE
DCOM- 19970501
LR  - 20190826
IS  - 0891-5849 (Print)
IS  - 0891-5849 (Linking)
VI  - 21
IP  - 2
DP  - 1996
TI  - In vivo indices of oxidative stress in lead-exposed C57BL/6 mice are reduced by 
      treatment with meso-2,3-dimercaptosuccinic acid or N-acetylcysteine.
PG  - 157-61
AB  - Knowledge of lead's capacity to disrupt the prooxidant/antioxidant balance within 
      mammalian tissues suggests that definitive therapy for chronic lead poisoning 
      should encompass both chelating and antioxidant actions. The dithiol 
      meso-2,3-Dimercaptosuccinic Acid (DMSA) is the first orally administered metal 
      chelating agent to receive U.S. Food and Drug Administration (FDA) approval for 
      the treatment of childhood plumbism and possesses the potential to function as an 
      antioxidant by removing lead from the site of deleterious oxidation reactions. 
      Five weeks of lead exposure was found to deplete glutathione (GSH) levels, 
      increase oxidized glutathione (GSSG), and promote malondialdehyde (MDA) 
      production in both liver and brain samples taken from C57BL/6 mice. GSH levels 
      increased and GSSG and MDA levels decreased in groups of lead-exposed mice that 
      received 1 mmol/kg DMSA or 5.5 mmol/kg N-acetylcysteine (NAC) for 7 d prior to 
      sacrifice. Treatment with DMSA caused a reduction in blood, liver, and brain lead 
      levels consistent with its function as a chelating agent, while treatment with 
      NAC did not reduce these lead levels. However, NAC did cause a reduction in 
      indices of oxidative stress in both brain and liver samples, which implies that 
      this synthetic thiol-containing antioxidant is capable of abrogating lead-induced 
      oxidative stress in vivo. Overall, these results suggest that lead-induced 
      oxidative stress in vivo can be mitigated by pharmacologic interventions, which 
      encompass both chelating as well as thiol-mediated antioxidant functions.
FAU - Ercal, N
AU  - Ercal N
AD  - Department of Chemistry, University of Missouri-Rolla 65401, USA.
FAU - Treeratphan, P
AU  - Treeratphan P
FAU - Hammond, T C
AU  - Hammond TC
FAU - Matthews, R H
AU  - Matthews RH
FAU - Grannemann, N H
AU  - Grannemann NH
FAU - Spitz, D R
AU  - Spitz DR
LA  - eng
GR  - R01HL51469/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 2P299V784P (Lead)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - DX1U2629QE (Succimer)
RN  - GAN16C9B8O (Glutathione)
RN  - K848JZ4886 (Cysteine)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/*pharmacology
MH  - Animals
MH  - Brain/metabolism
MH  - Cysteine/metabolism
MH  - Glutathione/metabolism
MH  - Lead/blood/metabolism/*toxicity
MH  - Liver/metabolism
MH  - Male
MH  - Malondialdehyde/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oxidation-Reduction
MH  - Oxidative Stress/*drug effects
MH  - Succimer/*pharmacology
EDAT- 1996/01/01 00:00
MHDA- 1996/01/01 00:01
CRDT- 1996/01/01 00:00
PHST- 1996/01/01 00:00 [pubmed]
PHST- 1996/01/01 00:01 [medline]
PHST- 1996/01/01 00:00 [entrez]
AID - 0891584996000202 [pii]
AID - 10.1016/0891-5849(96)00020-2 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 1996;21(2):157-61. doi: 10.1016/0891-5849(96)00020-2.