Quinone and oxyradical scavenging properties of N-acetylcysteine prevent dopamine mediated inhibition of Na+, K+-ATPase and mitochondrial electron transport chain activity in rat brain: Implications in the neuroprotective therapy of Parkinson's disease

Dopamine oxidation products such as H₂O₂ and reactive quinones have been held responsible for various toxic actions of dopamine, which have implications in the aetiopathogenesis of Parkinson's disease. This study has shown that N-acetylcysteine (0.25–1 mm) is a potent scavenger of both H₂O₂ and toxic quinones derived from dopamine and it further prevents dopamine mediated inhibition of Na⁺,K⁺-ATPase activity and mitochondrial respiratory chain function. The quinone scavenging ability of N-acetylcysteine is presumably related to its protective effect against dopamine mediated inhibition of mitochondrial respiratory chain activity. However, both H₂O₂ scavenging and quinone scavenging properties of N-acetylcysteine probably account for its protective effect against Na⁺,K⁺-ATPase inhibition induced by dopamine. The results have important implications in the neuroprotective therapy of sporadic Parkinson's disease since inactivation of mitochondrial respiratory activity and Na⁺,K⁺-ATPase may trigger intracellular damage pathways leading to the death of nigral dopaminergic neurons.