Quinolinic acid: neurotoxin or oxidative stress modulator?
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.
Department of Ecogenomics and Systems Biology, Division of Molecular Systems Biology, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, Vienna A-1090, Austria. vladimir.chobot@univie.ac.at.
Lenka
L
Kubicova
Franz
F
Hadacek
Vladimir
V
Chobot
D059165:Hormesis / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D007501:Iron / Q000737:chemistry* / Q000378:metabolism; D007737:Kynurenine / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D017378:Quinolinic Acid / Q000494:pharmacology / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism*
C045076:Fenton's reagent; D009498:Neurotoxins; D017382:Reactive Oxygen Species; D007737:Kynurenine; D006861:Hydrogen Peroxide; D007501:Iron; D017378:Quinolinic Acid