Manganese neurotoxicity and the role of reactive oxygen species.

Manganese (Mn) is an essential dietary nutrient, but an excess or accumulation can be toxic. Disease states, such as manganism, are associated with overexposure or accumulation of Mn and are due to the production of reactive oxygen species, free radicals, and toxic metabolites; alteration of mitochondrial function and ATP production; and depletion of cellular antioxidant defense mechanisms. This review focuses on all of the preceding mechanisms and the scientific studies that support them as well as providing an overview of the absorption, distribution, and excretion of Mn and the stability and transport of Mn compounds in the body.

An analysis of the effects of Mn2+ on oxidative phosphorylation in liver, brain, and heart mitochondria using state 3 oxidation rate assays.

Manganese (Mn) toxicity is partially mediated by reduced ATP production. We have used oxidation rate assays--a measure of ATP production--under rapid phosphorylation conditions to explore sites of Mn(2+) inhibition of ATP production in isolated liver, brain, and heart mitochondria. This approach has several advantages.

Speciation of manganese in cells and mitochondria: a search for the proximal cause of manganese neurotoxicity.

Recent studies of speciation of manganese (Mn) in brain mitochondria, neuron-like cells, and astrocytes are reviewed. No evidence is found for oxidation of Mn(2+) complexes to a Mn(3+) complex. The only evidence for any Mn(3+) complex is found in a spectrum essentially identical to that of mitochondrial manganese superoxide dismutase (MnSOD).

Determination of the oxidation states of manganese in brain, liver, and heart mitochondria.

Excess brain manganese can produce toxicity with symptoms that resemble those of Parkinsonism and causes that remain elusive. Manganese accumulates in mitochondria, a major source of superoxide, which can oxidize Mn2+ to the powerful oxidizing agent Mn3+. Oxidation of important cell components by Mn3+ has been suggested as a cause of the toxic effects of manganese.

XANES spectroscopy: a promising tool for toxicology: a tutorial.

X-ray absorption near edge structure (XANES) spectroscopy can provide information on the oxidation state of metal ions within a biological sample and also the complexes in which it is found. This type of information could be of great use to toxicologists in understanding the mechanism of action of many toxic agents. The prospect of using a sophisticated physical technique such as XANES may be somewhat intimidating for those without a strong physical background.