2,3-Dimercaptopropanol, 2,3-dimercaptopropane-1-sulfonic acid and meso-2,3-dimercaptosuccinic acid increase lead-induced inhibition of δ-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 δ-aminolevulinate dehydratase (δ-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 δ-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 δ-ALA-D activity was significantly inhibited (62%) by lead acetate. Lead acetate (1–1000 μM) pre-incubated with human blood increased the inhibitory potency of this compound on δ-ALA-D when compared to the assay without pre-incubation (89%). Chelating agents caused a marked potentiation of δ-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 δ-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.