Bull. Environ. Contam. Toxicol. (1996) 57:47-53 © 1996 Springer-Verlag New York Inc. δ -Aminolevulinic Acid Dehydratase Activity in Weanling and Adult Rats Exposed to Lead Acetate A. L. S. Ro d rig ue s, 1 J. B. T. Ro c ha , 2 M. E. Pe re ira , 2 D. O. So uza 3 1 Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil 2 Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97119-900, Santa Maria, RS, Brazil 3 Departamento de Bioquímica, lnstituto de Biociências, Universidade Federal do Rio Grande do Sul, 90046-900, Porto Alegre, RS, Brazil Received: 11 September 1995/Accepted: 9 February 1996 Lead is an environmental pollutant with no known beneficial health effects, and environmental or occupational exposure to this metal is known to result in toxicity. It may affect numerous organ systems, including the renal, reticuloendothelial, reproductive, and nervous system (Al Saleh 1994). Children and young animals are particularly sensitive to the toxic effects of this metal, being the central nervous system the main target of lead toxicity. Adults seem to be more resistant to lead neurotoxicity, but lead nephrotoxicity is a prominent effect (Nolan and Shaikh 1992). Lead inhibition of δ -aminolevulinic acid dehydratase (ALAD), a sulfhydryl enzyme of the heme-biosynthesis pathway, has been implicated in the pathogenesis of lead poisoning, since various critical cellular processes are affected by a reduced concentration of heme. Several studies suggest that neurotoxicity associated with lead exposure result from depletion of heme (for review, see Goering 1993). In addition, the substrate of the enzyme, δ- aminolevulinate (ALA), which accumulates in lead poisoning, has been proposed to be responsible, at least in part, for lead neurotoxicity by generating active oxygen species (Bechara et al. 1993). Several studies concerning inhibition of ALAD activity by lead have been conducted, especially in erythrocytes of various animal species (Granick et al. 1973, Rodrigues et al. 1989, Simmonds et al. 1995). ALAD reactivation index by the SH-reducing compound dithiothreitol (DTT) has also been reported to be a very sensitive parameter to evaluate ALAD inactivation (Granick et al. 1973, Sakai et al. 1980). Literature on ALAD specific activity in lead-exposed animals have mainly measured the activity of the enzyme in blood, kidney, and liver. Few studies have investigated cerebral ALAD activity in lead-exposed animals and the results reveal an insensitivity of brain ALAD to lead action (Oskarsson 1989, Rocha et al. 1995). However, in these studies lead exposure had been imposed during relatively short periods, which may not be of sufficient duration to cause an effect on the enzyme. Moreover some studies suggest that a cerebral lead-binding protein might reduce cerebral ALAD inhibition in lead-exposed animals by lowering the intracellular availability of Correspondence to: A. L. S. Rodrigues 47