Pro-oxidant DNA breakage induced by the interaction of L-DOPA with Cu(II): a putative mechanism of neurotoxicity.

Abstract

There are reports in scientific literature that the concentration of copper ions in Parkinsonian brain is at a level that could promote oxidative DNA damage. The possibility of copper chelation by antioxidants excited us to explore the generation of reactive oxygen species (ROS) and DNA damage by the interaction of L-DOPA with Cu(II) ions. In the present manuscript, L-DOPA was tested for its ability to bind with Cu(II) and reduce it to Cu(I). The generation of ROS, such as superoxide anion (O(2)(-)) and hydroxyl radical (OH(•)), was also ascertained. As a result of L-DOPA and Cu(II) interaction, the generation of O(2)(-) was found to be increased in a time-dependent manner. Moreover, the formation of OH(•) was also found to be enhanced with increasing concentrations of L-DOPA. Furthermore, Comet assay results clearly showed significantly higher cellular DNA breakage in lymphocytes treated with L-DOPA and Cu(II) as compared to those that were treated with L-DOPA alone. However, such DNA degradation was inhibited to a significant extent by scavengers of ROS and neocuproine, a membrane permeable Cu(I)-specific sequestering agent. These findings demonstrate that L-DOPA exhibits a pro-oxidant activity in the presence of copper ions.