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Quinolinic Acid: Neurotoxin or Oxidative Stress Modulator?
Department of Ecogenomics and Systems Biology, Division of Molecular Systems Biology, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, Vienna A-1090, Austria
Albrecht-von-Haller Institut, Plant Biochemistry, Georg-August-Universität Göttingen, Justus-von-Liebig-Weg 11, Göttingen D-37077, Germany
* Author to whom correspondence should be addressed.
Received: 2 September 2013; in revised form: 2 October 2013 / Accepted: 22 October 2013 / Published: 25 October 2013
Abstract: Quinolinic acid (2,3-pyridinedicarboxylic acid, QUIN) is a well-known neurotoxin. Consequently, QUIN could produce reactive oxygen species (ROS). ROS are generated in reactions catalyzed by transition metals, especially iron (Fe). QUIN can form coordination complexes with iron. A combination of differential pulse voltammetry, deoxyribose degradation and Fe(II) autoxidation assays was used for explorating ROS formation in redox reactions that are catalyzed by iron in QUIN-Fe complexes. Differential pulse voltammetry showed an anodic shift of the iron redox potential if iron was liganded by QUIN. In the H2O2/FeCl3/ascorbic acid variant of the deoxyribose degradation assay, the dose-response curve was U-shaped. In the FeCl3/ascorbic acid variant, QUIN unambiguously showed antioxidant effects. In the Fe(II) autoxidation assay, QUIN decreased the rate of ROS production caused by Fe(II) oxidation. Our study confirms that QUIN toxicity may be caused by ROS generation via the Fenton reaction. This, however, applies only for unnaturally high concentrations that were used in attempts to provide support for the neurotoxic effect. In lower concentrations, we show that by liganding iron, QUIN affects the Fe(II)/Fe(III) ratios that are beneficial to homeostasis. Our results support the notion that redox chemistry can contribute to explaining the hormetic dose-response effects.
Keywords: differential pulse voltammetry; Fenton reaction; hormesis; hydroxyl radical; inflammation; iron autoxidation; kynurenines; neuropathology; neurotoxicants; oxidative stress
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MDPI and ACS Style
Kubicova, L.; Hadacek, F.; Chobot, V. Quinolinic Acid: Neurotoxin or Oxidative Stress Modulator? Int. J. Mol. Sci. 2013, 14, 21328-21338.
Kubicova L, Hadacek F, Chobot V. Quinolinic Acid: Neurotoxin or Oxidative Stress Modulator? International Journal of Molecular Sciences. 2013; 14(11):21328-21338.
Kubicova, Lenka; Hadacek, Franz; Chobot, Vladimir. 2013. "Quinolinic Acid: Neurotoxin or Oxidative Stress Modulator?" Int. J. Mol. Sci. 14, no. 11: 21328-21338.