Glutathione antioxidant system and methylmercury-induced neurotoxicity: An intriguing interplay

• Published in: Biochimica et biophysica acta. General subjects Vol. 1863; no. 12; p. 129285
• Main Authors: Farina, Marcelo, Aschner, Michael
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2019
• Subjects: Animals; Antioxidant system; antioxidants; Antioxidants - metabolism; aquatic ecosystems; aquatic environment; central nervous system; enzymes; fish; food chain; Glutathione; Glutathione - metabolism; Humans; Lewis acids; Lewis bases; mercury; methylation; Methylmercury; methylmercury compounds; Methylmercury Compounds - pharmacokinetics; Methylmercury Compounds - toxicity; microorganisms; Neurotoxicity; Neurotoxicity Syndromes - embryology; Neurotoxicity Syndromes - metabolism; Neurotoxins - pharmacokinetics; Neurotoxins - toxicity; oxidative stress; Oxidative Stress - drug effects; piscivores; postpartum period; proteins; Selenols; Thiols; toxic substances; Antioxidant system; Neurotoxicity; Thiols; Selenols; Methylmercury; Glutathione
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2019.01.007

Methylmercury (MeHg) is a toxic chemical compound naturally produced mainly in the aquatic environment through the methylation of inorganic mercury catalyzed by aquatic microorganisms. MeHg is biomagnified in the aquatic food chain and, consequently, piscivorous fish at the top of the food chain possess huge amounts of MeHg (at the ppm level). Some populations that have fish as main protein's source can be exposed to exceedingly high levels of MeHg and develop signs of toxicity. MeHg is toxic to several organs, but the central nervous system (CNS) represents a preferential target, especially during development (prenatal and early postnatal periods). Though the biochemical events involved in MeHg-(neuro)toxicity are not yet entirely comprehended, a vast literature indicates that its pro-oxidative properties explain, at least partially, several of its neurotoxic effects. As result of its electrophilicity, MeHg interacts with (and oxidize) nucleophilic groups, such as thiols and selenols, present in proteins or low-molecular weight molecules. It is noteworthy that such interactions modify the redox state of these groups and, therefore, lead to oxidative stress and impaired function of several molecules, culminating in neurotoxicity. Among these molecules, glutathione (GSH; a major thiol antioxidant) and thiol- or selenol-containing enzymes belonging to the GSH antioxidant system represent key molecular targets involved in MeHg-neurotoxicity. In this review, we firstly present a general overview concerning the neurotoxicity of MeHg. Then, we present fundamental aspects of the GSH-antioxidant system, as well as the effects of MeHg on this system. •MeHg is toxic to several organs, but the CNS represents a preferential target, especially during development.•MeHg interacts with (and oxidize) nucleophilic groups present in proteins or low-molecular weight molecules.•GSH and enzymes belonging to the GSH antioxidant system represent molecular targets involved in MeHg-neurotoxicity.•MeHg x GSH or MeHg x GPxs interaction decreases the cellular capacity to detoxify oxidants, favoring toxicity.•MeHg excretion is significantly favored by its interaction with GSH.