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Open AccessArticle

Astaxanthin Counteracts Excitotoxicity and Reduces the Ensuing Increases in Calcium Levels and Mitochondrial Reactive Oxygen Species Generation

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Laboratory of Cellular and Molecular Plasticity, Department of Pathology and Physiology, Medical School, Faculty of Medicine, Universidad de Valparaíso, Valparaíso 2341386, Chile
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Translational Neurology Center, Faculty of Medicine, Universidad de Valparaíso, Valparaíso 2341386, Chile
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Biomedical Research Center, Universidad de Valparaíso, Valparaíso 2341386, Chile
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Biomedical Neuroscience Institute, Faculty of Medicine, Universidad de Chile, Santiago 8380000, Chile
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Department of Technology and Pharmaceutical Sciences, Faculty of Chemical and Pharmaceutical Sciences, Advanced Center for Chronic Diseases (ACCDiS), Universidad de Chile, Santos Dumont 964, Independencia, Santiago 8380494, Chile
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Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany
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Centro Integrativo de Biología y Química Aplicada (CIBQA), Universidad Bernardo O’Higgins, Santiago 8370854, Chile
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Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago 8380000, Chile
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Interdisciplinary Center of Neuroscience of Valparaíso, Universidad de Valparaíso, Valparaíso 2381850, Chile
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Interdisciplinary Center for Health Studies, Universidad de Valparaíso, Valparaíso 2341386, Chile
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Department of Neurosciences and Program of Physiology and Biophysics, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago 8380000, Chile
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Center for Exercise, Metabolism and Cancer Studies, Faculty of Medicine, Universidad de Chile, Santiago 8380000, Chile
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Authors to whom correspondence should be addressed.
Mar. Drugs 2020, 18(6), 335; https://doi.org/10.3390/md18060335
Received: 18 April 2020 / Revised: 28 May 2020 / Accepted: 8 June 2020 / Published: 26 June 2020
(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)
Astaxanthin (ASX) is a carotenoid pigment with strong antioxidant properties. We have reported previously that ASX protects neurons from the noxious effects of amyloid-β 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 from N-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. View Full-Text
Keywords: NMDA; astaxanthin; calcium; mitochondrial superoxide; excitotoxicity NMDA; astaxanthin; calcium; mitochondrial superoxide; excitotoxicity
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García, F.; Lobos, P.; Ponce, A.; Cataldo, K.; Meza, D.; Farías, P.; Estay, C.; Oyarzun-Ampuero, F.; Herrera-Molina, R.; Paula-Lima, A.; Ardiles, Á.O.; Hidalgo, C.; Adasme, T.; Muñoz, P. Astaxanthin Counteracts Excitotoxicity and Reduces the Ensuing Increases in Calcium Levels and Mitochondrial Reactive Oxygen Species Generation. Mar. Drugs 2020, 18, 335.

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