2,3-Dimercaptopropanol, 2,3-dimercaptopropane-1-sulfonic acid and meso-2,3-dimercaptosuccinic acid increase lead-induced inhibition of delta-aminolevulinate dehydratase in vitro and ex vivo.
We investigated the effects of dimercaprol (BAL), meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercapto-1-propanesulphonic acid (DMPS) on human blood delta-aminolevulinate dehydratase (delta-ALA-D) activity, the most reliable indicator of lead intoxication in humans, in the presence of lead in vitro. Furthermore, we studied the effects of the chelating agents, administered subcutaneously, on delta-ALA-D activity in blood and tissues of mice submitted to sub-acute lead exposure (50 mg/kg for 15 consecutive days, subcutaneously). In vitro results demonstrated that human blood delta-ALA-D activity was significantly inhibited (62%) by lead acetate. Lead acetate (1-1000 microM) pre-incubated with human blood increased the inhibitory potency of this compound on delta-ALA-D when compared to the assay without pre-incubation (89%). Chelating agents caused a marked potentiation of delta-ALA-D inhibition induced by lead, in vitro. One of the most notable observations in the present study was the correspondence between in vitro and ex vivo effects. In fact, BAL and DMPS increase the inhibitory effect of lead on delta-ALA-D activity from mice blood. The complexes formed (lead and chelators) were more inhibitory than lead alone in kidney and liver enzyme activity, ex vivo.
Santos
F W
FW
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Av. Roraima CCNE, Predio 18, CEP 97105-900, Santa Maria, RS, Brazil. francielliweber@yahoo.com.br
Rocha
J B T
JB
Nogueira
C W
CW
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002614:Chelating Agents / Q000494:pharmacology*; D004112:Dimercaprol / Q000494:pharmacology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D007854:Lead / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors*; D004113:Succimer / Q000494:pharmacology*; D014494:Unithiol / Q000494:pharmacology*
D002614:Chelating Agents; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D004112:Dimercaprol; D007854:Lead; D014494:Unithiol; D004113:Succimer; D000623:Porphobilinogen Synthase