Lead Exposure and Ethanol Intake: Oxidative Stress as a Converging Mechanism of Action

Abstract Lead (Pb) exposure and ethanol (EtOH) abuse coexist in western societies. The ubiquity of Pb as an environmental contaminant and socially accepted EtOH intake prompted us to unravel any potentiated effects and search for shared mechanisms of action. This chapter presents evidence of clinical and experimental effects that underline the importance of concurrent exposure, including the potentiated toxicity of early-life exposure. Oxidative stress is proposed as a common mechanism, based on well-described studies of individual and combined redox effects. Furthermore, Pb potentiation of the motivational properties of EtOH is explained by brain EtOH metabolism, with catalase (CAT) and aldehyde dehydrogenase-2 (ALDH2) as key enzymes in the redox imbalance in the central nervous system (CNS). Evidence is provided that CAT with its dual characteristics, that is, as an antioxidant and an EtOH-metabolizing function, and ALDH2 with its mitochondrial localization and NAD + /NADH ratio disruption, have a preponderant role in the potentiation of Pb/EtOH toxicity and the pharmacological effects of EtOH.