Abstract
Kynurenic acid (KYNA) and quinolinic acid (QUIN) are metabolites formed in the degradation of tryptophan (Trp). QUIN is a selective NMDA receptor antagonist and may exert neurotoxic effects, whereas KYNA is an agonist of glutamatergic and cholinergic receptors and presents antioxidant properties. KYNA/QUIN ratio is decreased in several central nervous system disorders, but the mechanisms involved are not well elucidated. In the present study, we try to determine the neuroprotective capacity of KYNA on the QUIN effects in redox homeostasis changes (H2DCF oxidation, superoxide dismutase/catalase (SOD/CAT) ratio, glutathione peroxidase (GPx) activity, sulfhydryl content, and nitrite levels), as well as on inflammatory parameters (levels of TNF-α, IL-1β, and IL-6). KYNA and QUIN effects on the activities of Na+,K+-ATPase and acetylcholinesterase (AChE) were also evaluated. Thirty-day-old male Wistar rats underwent stereotactic surgery and received intrastriatal injections as follows: group 1—control (PBS-injected), group 2—KYNA (100 μM), group 3—QUIN (150 nM), and group 4—KYNA + QUIN (KYNA-injected followed QUIN-injected). Results demonstrated that the KYNA administration was able to prevent the increase in reactive oxygen species, SOD/CAT ratio, and pro-inflammatory cytokines (IL-1β and IL-6) and the decrease in GPx activity, sulfhydryl content, and nitrite levels caused by QUIN. KYNA was also able to partially prevent the decrease in Na+,K+-ATPase activity and the increase in AChE activity caused by QUIN. This study may help in the elucidation of neuroprotective effects of KYNA against oxidative and inflammatory insults caused by QUIN in the striatum of young male Wistar rats.
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Funding
This work was supported by Universal Edital (401507/2016)/Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-Brazil), INCT (EN 465671/2014-4)/Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) – Brazil and PRONEX(16/2551-0000465-0)/Fundação de Amparo à Pesquisa do Rio Grande do Sul (FAPERGS).
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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 (11.794/2008) and the experimental protocol was approved by the University Ethics Committee (CEUA) under the project #31435.
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Ferreira, F.S., Schmitz, F., Marques, E.P. et al. Intrastriatal Quinolinic Acid Administration Impairs Redox Homeostasis and Induces Inflammatory Changes: Prevention by Kynurenic Acid. Neurotox Res 38, 50–58 (2020). https://doi.org/10.1007/s12640-020-00192-2
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DOI: https://doi.org/10.1007/s12640-020-00192-2