PMID- 12499112
OWN - NLM
STAT- MEDLINE
DCOM- 20030318
LR  - 20220330
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 184
IP  - 2-3
DP  - 2003 Mar 3
TI  - 2,3-Dimercaptopropane-1-sulfonic acid and meso-2,3-dimercaptosuccinic acid 
      increase mercury- and cadmium-induced inhibition of delta-aminolevulinate 
      dehydratase.
PG  - 85-95
AB  - Compounds derived from Dimercaprol, such as meso-2,3-dimercaptosuccinic acid 
      (DMSA) and 2,3-dimercaptopropane-1-sulfonic acid (DMPS), are becoming common 
      agents for treating humans exposed to heavy metals. Heavy metals such as Pb(2+), 
      Hg(2+) and Cd(2+) can inhibit delta-aminolevulinate dehydratase (delta-ALA-D) 
      activity. Delta-ALA-D catalyzes the condensation of two delta-aminolevulinic acid 
      (delta-ALA) molecules with the formation of porphobilinogen, a heme precursor. 
      The effects of DMSA and DMPS alone or in combination with Cd(2+), Hg(2+), or 
      Pb(2+) on hepatic delta-ALA-D were examined. DMPS and DMSA caused a 
      dose-dependent inhibition of hepatic delta-ALA-D. In the presence of Hg(2+) or 
      Cd(2+) the inhibitory potency of DMPS increased. Similarly, the inhibitory 
      effects of Hg(2+) and Cd(2+) were markedly increased in the presence of DMSA. In 
      contrast, the inhibitory effect of DMPS was not changed by inclusion of Pb(2+). 
      As observed with DMSA, Zn(2+) did not modified the inhibitory effect of DMPS. 
      Data of the present report support the idea that the complexes formed 
      (metals-DMSA or DMPS) were more inhibitory than the metal (Hg(2+) and Cd(2+)) or 
      the chelating agent alone to the hepatic delta-ALA-D activity, in vitro. The 
      mechanism of hepatic delta-ALA-D inhibition by Hg(2+)-DMPS/DMSA and 
      Cd(2+)-DMPS/DMSA complexes involve the essential thiol groups of the enzyme.
FAU - Nogueira, C W
AU  - Nogueira CW
AD  - Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Universidade 
      Federal de Santa Maria, Santa Maria, RS, Brazil.
FAU - Soares, F A
AU  - Soares FA
FAU - Nascimento, P C
AU  - Nascimento PC
FAU - Muller, D
AU  - Muller D
FAU - Rocha, J B T
AU  - Rocha JB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Chelating Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - 00BH33GNGH (Cadmium)
RN  - 2P299V784P (Lead)
RN  - 4076-02-2 (Unithiol)
RN  - DX1U2629QE (Succimer)
RN  - EC 4.2.1.24 (Porphobilinogen Synthase)
RN  - FXS1BY2PGL (Mercury)
RN  - J41CSQ7QDS (Zinc)
SB  - IM
MH  - Animals
MH  - Cadmium/*pharmacology
MH  - Chelating Agents/*pharmacology
MH  - Drug Synergism
MH  - Enzyme Inhibitors/*pharmacology
MH  - Lead/pharmacology
MH  - Male
MH  - Mercury/*pharmacology
MH  - Mice
MH  - Polarography
MH  - Porphobilinogen Synthase/*antagonists & inhibitors/isolation & purification
MH  - Succimer/*pharmacology
MH  - Unithiol/*pharmacology
MH  - Zinc/physiology
EDAT- 2002/12/25 04:00
MHDA- 2003/03/19 04:00
CRDT- 2002/12/25 04:00
PHST- 2002/12/25 04:00 [pubmed]
PHST- 2003/03/19 04:00 [medline]
PHST- 2002/12/25 04:00 [entrez]
AID - S0300483X02005759 [pii]
AID - 10.1016/s0300-483x(02)00575-9 [doi]
PST - ppublish
SO  - Toxicology. 2003 Mar 3;184(2-3):85-95. doi: 10.1016/s0300-483x(02)00575-9.