Quinolinic Acid: An Endogenous Neurotoxin with Multiple Targets
Table 1
Effect of various molecules on the toxicity induced by QUIN.
Compound
Mechanism of action
Reference
Melatonin
(i) Attenuates the convulsant effect of quinolinate (ii) Partially protects against the increase of circling behavior (iii) Protects against the increase in ROS and protein carbonyl levels as well as the inhibition of superoxide dismutase activity
(i) Attenuates the QUIN-induced early reactive oxygen species formation and lipid peroxidation (ii) Prevents loss of mitochondrial reductive capacity and morphological alterations in the striatum (iii) Induces stimulation of striatal GPx activity (iv) Prevents IB- degradation (v) Reduces the nuclear translocation of NF-B and inhibits the activity of caspase-3, resulting in internucleosomal DNA preservation (vi) Induces an early stimulation of TrxR activity
(i) Significantly improve body weight, locomotor activity, oxidative defense, activity of mitochondrial enzyme complex, rotarod performance, and balance beam walk
(i) Improves body weight, behavioral alterations (locomotor activity and rotarod performance) and attenuates oxidative damage and mitochondrial enzymes complexes dysfunction (ii) Improves learning task in rats receiving chronic i.c.v, infusion of QUIN (iii) Decreases release of lactate dehydrogenase (LDH) in NSC-34 cells after 48 h of QUIN
(i) Significantly attenuates QUIN-mediated PARP activation, NAD+ depletion, and LDH release in both neurons and astrocytes as well as decreases LDH release in NSC-34 cells induced by QUIN
(i) Reduce lipid peroxidation (ii) Prevent mitochondrial dysfunction in brain synaptosomes (iii) Attenuate the behavioral alterations and striatal degeneration
(i) Reduce the generation of superoxide anions (ii) Reduce the lipid peroxidation after an intrahippocampal injection of QUIN (iii) Reduce the spatial memory deficit
Iron metalloporphyrins such as Fe(TPFPP) and Fe(TPPS)
(i) Decrease 3-nitrotyrosine levels (ii) Prevent lipid peroxidation and mitochondrial dysfunction (iii) Reduce the DNA fragmentation and decreases caspase-3-like activation (iv) Abolish the circling behavior (v) Partially recover GABA levels (vi) Reduce the immunochemical expression of IL-6 and iNOS
(i) Inhibit QUIN-induced nNOS activity and subsequent nitrite production (ii) Reduce 3-nitrotyrosine production (iii) Prevent DNA damage and PARP-1 activation (iv) Attenuate QUIN-induced Ca2+ influx