Neurotoxic significance of H2O2 generation in nigral dopaminergic damage by paraquat and protective action of effusol and dehydroeffusol, Juncus effusus ingredients.

Abstract

H₂O₂ generation by paraquat (PQ) leads to accumulating glutamate in the nigral extracellular compartment and then excessive influx of extracellular Zn²⁺ by AMPA receptor activation, resulting in dopaminergic cell death. Here we tested a postulation that the strategy for inactivating H₂O₂ generation by PQ protects dopaminergic neurons. Either HYDROP for capturing intracellular H₂O₂ or HYDROP-EX for capturing extracellular H₂O₂ was co-injected with PQ into the rat substantia nigra pars compacta (SNpc) and dopaminergic damage was determined by tyrosine hydroxylase (TH) immunostaining. The decrease in SNpc TH stain was avoided by co-injection. The effect of HYDROP-EX supports the previous evidence that intracellular H₂O₂ generated by PQ through dopamine transporters is transported to the extracellular compartment and linked with the decrease in TH stain. Furthermore, we tested the effect of effusol and dehydroeffusol, unique phenanthrene ingredients in Juncus effusus. The decrease in SNpc TH stain was also avoided in the presence of effusol or dehydroeffusol. Effusol suppressed both PQ-induced accumulations of extracellular glutamate and intracellular H₂O₂. In contrast, dehydroeffusol did not suppress accumulation of extracellular glutamate, but suppressed accumulation of intracellular H₂O₂. This paper first indicates neurotoxic significance of PQ-mediated H₂O₂ generation at nigral glutamatergic-dopaminergic synapses. Effusol and dehydroeffusol may protect dopaminergic neurons via reducing H₂O₂ generation by PQ.