Manganese exposure and induced oxidative stress in the rat brain

Neurotoxicity linked to excessive brain manganese levels can occur as a result of high level Mn exposures and/or metabolic aberrations (liver disease and decreased biliary excretion). Increased brain manganese levels have been reported to induce oxidative stress, as well as alterations in neurotransmitter metabolism with concurrent neurobehavioral and motor deficits. Two putative mechanisms in which manganese can produce oxidative stress in the brain are: (1) via its oxidation of dopamine, and (2) interference with normal mitochondrial respiration. Measurements of antioxidant species (e.g., glutathione and metallothionein), and the abundance of proteins (enzymes) exquisitely sensitive to oxidation (e.g., glutamine synthetase) have been commonly used as biomarkers of oxidative stress, particularly in rat brain tissue. This paper examines the link between manganese neurotoxicity in the rat brain and common pathways to oxidative stress. (C) 2004 Published by Elsevier B.V.