Quinolinic acid induces oxidative stress in rat brain synaptosomes

Abstract

The oxidative action of quinolinic acid (QUIN), and the protective effects of glutathione (GSH), and 2-amino-5-phosphonovaleric acid (APV), were tested in rat brain synaptosomes, Reactive oxygen species (ROS) formation was quantified after the exposure of synaptosomes to increasing concentrations of QUIN (25-500 microM). The potency of QUIN to induce lipid peroxidation (LP) was tested as a regional index of thiobarbituric acid-reactive substances (TBARS) production, and the antioxidant actions of both GSH (50 microM) and APV (250 microM) on QUIN-induced LP were evaluated in synaptosomes prepared from different brain regions. QUIN induced concentration-dependent increases in ROS formation and TBARS in all regions analyzed, but increased production of fluorescent peroxidized lipids only in the striatum and the hippocampus, whereas both GSH and APV decreased this index. These results suggest that the excitotoxic action of QUIN involves regional selectivity in the oxidative status of brain synaptosomes, and may be prevented by substances exhibiting antagonism at the NMDA receptor.

Quinolinic acid induces NMDA receptor-mediated lipid peroxidation in rat brain microvessels

“…That is, unless such action of QUIN can be causally linked to an additional process such as lipid peroxidation that has a definite potential to compromise the capillary barrier. 19 The results of the present study strongly imply that QUIN can, indeed, cause lipid peroxidation in brain microvessels. There could be regional variations in the exact mechanism of the action of QUIN: in comparison to hippocampus and the entorhinal cortex, the lipid peroxidation in the striatum was less sensitive to the NMDA-R antagonist D-2-APV, possibly suggesting the presence of an NMDA-R independent component of the mechanism (Table 1; see Pláteník et al 20 for an example of such mechanism).…”

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