Kynurenic Acid Restores Nrf2 Levels and Prevents Quinolinic Acid-Induced Toxicity in Rat Striatal Slices

  • Fernanda Silva Ferreira
  • Helena Biasibetti-Brendler
  • Paula Pierozan
  • Felipe Schmitz
  • Carolina Gessinger Bertó
  • Caroline Acauan Prezzi
  • Vanusa Manfredini
  • Angela T. S. Wyse
Article
  • 138 Downloads

Abstract

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.

Keywords

Kynurenic acid Quinolinic acid Nrf2 Oxidative status Mitochondrial function 

Notes

Funding Information

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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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Fernanda Silva Ferreira
    • 1
    • 2
  • Helena Biasibetti-Brendler
    • 2
  • Paula Pierozan
    • 2
  • Felipe Schmitz
    • 1
    • 2
  • Carolina Gessinger Bertó
    • 2
  • Caroline Acauan Prezzi
    • 2
  • Vanusa Manfredini
    • 3
  • Angela T. S. Wyse
    • 1
    • 2
    • 4
  1. 1.Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, ICBSUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Laboratório de Neuroproteção e Doenças Neurometabólicas, Departamento de Bioquímica, ICBSUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  3. 3.Programa de Pós-Graduação em BioquímicaUniversidade Federal do PampaUruguaianaBrazil
  4. 4.Departamento de Bioquímica, ICBSUniversidade Federal do Rio Grande do SulPorto AlegreBrazil

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