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 α-(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 (III) 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.