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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 2371895, 12 pages
https://doi.org/10.1155/2017/2371895
Research Article

3-Hydroxykynurenine and 3-Hydroxyanthranilic Acid Enhance the Toxicity Induced by Copper in Rat Astrocyte Culture

1Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, S.S.A, 14269 México City, MEX, Mexico
2Biochemistry, Universidad Nacional Autónoma de México (UNAM), México City, MEX, Mexico
3Laboratorio de Neuroinmunología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, S.S.A, 14269 México City, MEX, Mexico

Correspondence should be addressed to Benjamín Pineda; moc.liamtoh@67oipneb and Verónica Pérez de la Cruz; xm.moc.oohay@depev

Received 24 March 2017; Accepted 11 June 2017; Published 31 July 2017

Academic Editor: Andrea Romani

Copyright © 2017 Daniela Ramírez-Ortega et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Copper is an integral component of various enzymes, necessary for mitochondrial respiration and other biological functions. Excess copper is related with neurodegenerative diseases as Alzheimer and is able to modify cellular redox environment, influencing its functions, signaling, and catabolic pathways. Tryptophan degradation through kynurenine pathway produces some metabolites with redox properties as 3-hydroxykynurenine (3-HK) and 3-hydroxyanthranilic acid (3-HANA). The imbalance in their production is related with some neuropathologies, where the common factors are oxidative stress, inflammation, and cell death. This study evaluated the effect of these kynurenines on the copper toxicity in astrocyte cultures. It assessed the CuSO4 effect, alone and in combination with 3-HK or 3-HANA on MTT reduction, ROS production, mitochondrial membrane potential (MMP), GHS levels, and cell viability in primary cultured astrocytes. Also, the chelating copper effect of 3-HK and 3-HANA was evaluated. The results showed that CuSO4 decreased MTT reduction, MMP, and GSH levels while ROS production and cell death are increasing. Coincubation with 3-HK and 3-HANA enhances the toxic effect of copper in all the markers tested except in ROS production, which was abolished by these kynurenines. Data suggest that 3-HK and 3-HANA increased copper toxicity in an independent manner to ROS production.