Kynurenic acid (KYNA) and quinolinic acid (QUIN) are metabolites produced in the degradation of tryptophan and have important neurological activities. KYNA/QUIN ratio changes are known to be associated with central nervous system disorders, such Alzheimer, Parkinson, and Huntington diseases. In the present study, we investigate the ability of KYNA in prevent the first events preceding QUIN-induced neurodegeneration in striatal slices of rat. We evaluated the protective effect of KYNA on oxidative status (reactive oxygen species production, antioxidant enzymes activities, lipid peroxidation, nitrite levels, protein and DNA damage, and iNOS immunocontent), mitochondrial function (mitochondrial mass, membrane potential, and respiratory chain enzymes), and Na+,K+-ATPase in striatal slices of rats treated with QUIN. Since QUIN alters the levels of Nrf2, we evaluated the influence of KYNA protection on this parameter. Striatal slices from 30-day-old Wistar rats were preincubated with KYNA (100 μM) for 15 min, followed by incubation with 100-μM QUIN for 30 min. Results showed that KYNA prevented the increase of ROS production caused by QUIN and restored antioxidant enzyme activities and the protein and lipid damage, as well as the Nrf2 levels. KYNA also prevented the effects of QUIN on mitochondrial mass and mitochondrial membrane potential, as well as the decrease in the activities of complex II, SDH, and Na+,K+-ATPase. We suggest that KYNA prevents changes in Nrf2 levels, oxidative imbalance, and mitochondrial dysfunction caused by QUIN in striatal slices. This study elucidates some of the protective effects of KYNA against the damage caused by QUIN toxicity.
Kynurenic acid Quinolinic acid Nrf2 Oxidative status Mitochondrial function
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This work was supported by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-Brazil).
Compliance with Ethical Standards
The ethical standards followed the official governmental guidelines issued by the Brazilian Federal of Societies for Experimental Biology, following the Guide for Care and Use of Laboratory Animals and Arouca Law (Law no. 11.794/2008) and the experimental protocol was approved by the University’s Ethics Committee (CEUA) under the project #31435.
Conflict of Interest
The authors declare that they have no conflict of interest.
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