Astaxanthin Counteracts Excitotoxicity And Reduces The Ensuing Increases In Calcium Levels And Mitochondrial Reactive Oxygen Species Generation

Astaxanthin (ASX) is a carotenoid pigment with strong antioxidant properties. We have reported previously thatASXprotects neurons fromthe noxious effects of amyloid-peptide oligomers, which promote excessive mitochondrial reactive oxygen species (mROS) production and induce a sustained increase in cytoplasmic Ca2+ concentration. These properties make ASX a promising therapeutic agent against pathological conditions that entail oxidative and Ca2+ dysregulation. Here, we studied whether ASX protects neurons fromN-methyl-D-Aspartate (NMDA)-induced excitotoxicity, a noxious process which decreases cellular viability, alters gene expression and promotes excessive mROS production. Incubation of the neuronal cell line SH-SY5Y with NMDA decreased cellular viability and increased mitochondrial superoxide production; pre-incubation with ASX prevented these effects. Additionally, incubation of SH-SY5Y cells with ASX effectively reduced the basal mROS production and prevented hydrogen peroxide-induced cell death. In primary hippocampal neurons, transfected with a genetically encoded cytoplasmic Ca2+ sensor, ASX also prevented the increase in intracellular Ca2+ concentration induced by NMDA.We suggest that, by preventing the noxious mROS and Ca2+ increases that occur under excitotoxic conditions, ASX could be useful as a therapeutic agent in neurodegenerative pathologies that involve alterations in Ca2+ homeostasis and ROS generation.