The Glutathionyl Radical Formation in the Reaction between Manganese and Glutathione and Its Neurotoxic Implications

"Electron spin resonance (ESR) spin trapping methodology has been used to study the reactions of manganese dusts with glutathione, employing a-{4-pyridyl-1-oxide)·N-tert-butyl-nitrone (PBN) and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as spin traps. The results show evidence for the glutathionyl radical formation in the reactions of both MnO2 and manganese (Ill) acetate with glutathione. Based on these experimental observations, we hypothesise that the mechanism of neurotoxic effects of manganese might be due to the fact that the generation of glutathionyl radicals depletes the glutathione pool and reduces the glutathione shield against free radical products of dopamine metabolism and manganese induced reactive oxygenated species. IntroductionExposure to manganese compounds often occurs as the result of foundries and mining operations (1. 2). Other significant sources of environmental manganese include coal-fired power plants and burning of residual and crude oil (3, 4). Lately gasoline combustion has also started to contribute since manganese (methyl cyclopentadienyl manganese tricarbonyl. 0. 125 g/gallon) is being used instead of lead as an antiknock ingredient in automobile fuels (5. 6). Although manganese is an essential element in certain biological processes it is toxic in excessive amounts. The manganese toxicity is mainly associated with the nervous system (7-9). Symptoms frequently observed in manganese poisoning or manganism are disorientation, memory loss, anxiety, compulsive laughing and crying, mask-like faces, akincsia rigidity and tremor (10). In spite of numerous investigations to understand the mechanism of manganese induced injury. it has not been possible to localize the initial chemical lesion responsible for altered physiology and ultimate cell death. This may perhaps he the reason for failure in developing a successful therapy for manganese intoxication."