Ebselen and diphenyl diselenide do not change the inhibitory effect of lead acetate on delta-aminolevulinate dehidratase

Abstract: It is known that lead is toxic to several species of animals, and growing data support the participation of oxidative in lead toxicity. Selenium compounds, like diphenyl diselenide and Ebselen have a thiol-peroxidase like and other antioxidant properties. In this work, we determine whether these non-thiol-containing compounds with antioxidant properties could reverse the toxicity produced by Pb2+. Lead acetate injection followed by injection with Ebselen or diphenyl diselenide did not change the levels of non-protein thiol groups (NPSH), whereas simultaneous treatment with lead plus Ebselen reduced NPSH levels in liver. Lead and Ebselen caused a marked reduction in TBARS level in kidney, whereas lead or selenium compounds did not change TBARS levels in brain or liver. Lead acetate inhibited, δ-aminolevulinate dehydratase (ALA-D) activity in blood, liver, kidney and brain. Selenium compounds did not change enzyme activity nor the inhibitory effect of lead acetate in kidney and liver. Ebselen reversed brain ALA-D inhibition caused by Pb2+. Reactivation index for ALA-D by DTT was higher in lead-treated groups than control groups in all tissues. Lead acetate or selenium compounds did not demonstrate alteration on [3H]-glutamate uptake by synaptosomes, whereas lead acetate plus Ebselen showed an increase on [3H]-glutamate uptake. The results of the present study indicate that ALA-D inhibition antecedes the overproduction of reactive oxygen species, which is becoming well documented in the literature. [Copyright &y& Elsevier]