Lead exposure and ethanol intake: oxidative stress as a converging mechanism of action

VIRGOLINI, MIRIAM B.; MATTALLONI, MARA S.; DEZA-PONZIO, ROMINA; ALBRECHT, PAULA A.; CANCELA, L. M.; PREEDY, VICTOR

Neuroscience of alcohol: mechanisms and treatment

Elsevier

Lugar: London; Año: 2018;

Pb exposure and EtOH abuse coexist in western societies. The ubiquity of Pb as an environmental contaminant and of socially accepted EtOH intake prompts 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 CAT and ALDH2 as key enzymes in the redox imbalance in the CNS. Evidence is provided that CAT with its dual characteristics, i.e. antioxidant and EtOH-metabolizing functions, 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.