Quinolinic acid: Neurotoxin or oxidative stress modulator?

Quinolinic acid (2,3-pyridinedicarboxylic acid, QUIN) is a well-known neurotoxin. Consequently, Quinolinic acid could produce reactive oxygen species (ROS). ROS are generated in reactions catalyzed by transition metals, especially iron (Fe). Quinolinic acid 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 Quinolinic acid-Fe complexes. Differential pulse voltammetry showed an anodic shift of the iron redox potential if iron was liganded by Quinolinic acid. In the H2O2/FeCl3/ascorbic acid variant of the deoxyribose degradation assay, \r<br />the dose-response curve was U-shaped. In the FeCl3/ascorbic acid variant, Quinolinic acid unambiguously showed antioxidant effects. In the Fe(II) autoxidation assay, Quinolinic acid decreased the rate of ROS production caused by Fe(II) oxidation. 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, Quinolinic acid affects the Fe(II)/Fe(III) ratios that are beneficial to homeostasis.