Neurotoxicity glutathione levels

MPTP decreases glutathione levels and increases the levels of reactive oxygen species and the degree of lipid peroxidation in mouse brain slices in vitro and increases the levels of reactive oxygen species in mouse brain in vivo. MPTP neurotoxicity in vitro is reduced by glutathione. In vitro studies have shown that MPP neurotoxicity can be reduced by vitamin E, vitamin C, coenzyme Q, and mannitol (but not by superoxide dismutase, catalase, allopurinol, or dimethyl sulfoxide). P-Carotene, vitamin C, and /V-acctylcystcine partially protect against the neurotoxic effects of MPTP in mice, as do nicotinamide, coenzyme Q, and the free-radical spin trap A-tert-butyl-a-(sulfophenyl) nitrone. 

Giordano G, Kavanagh TJ, Costa LG. Neurotoxicity of a polybrominated diphenyl ether mixture (DE-71) in mouse neurons and astrocytes is modulated by intracellular glutathione levels. Toxicol Appl Pharmacol. 2008 232 161-168. 

Allowing that the above transfer system involving Mn does occur, the cause of manganese neurotoxicity is still little understood. Archibald and Tyree [75] propose that the ability of to attack catecholamines indicates that this metal ion is toxic in itself, while other workers [76-78] see the toxicity as being due to a variety of causes such as autooxidation of dopamine, decreased glutathione (GSH) levels [64,79], reduced GSH peroxidase and brain catalase [79], and Mn -induced production either of toxic catecholamines and quinones [77] or of reactive oxo species such as superoxide, hydroxide radicals, or hydrogen peroxide [77,80,81]. A further excellent summary of much of the above detail is given by Donaldson and Barbeau [82]. 

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