Skip to main content
Log in

Quinolinic acid is a potent lipid peroxidant in rat brain homogenates

  • Original Articles
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

In this study, we describe the lipoperoxidative effect of quinolinic acid (QUIN) in vitro. The formation of thiobarbituric acid reactive products (TBA-RP), an index of lipid peroxidation, was measured in rat brain homogenates after incubation at 37°C for 30 min in the presence of QUIN and some structurally and metabolically related compounds such as Kynurenine, Kynurenic acid, Glutamate, Aspartate and Kainate. Concentrations of QUIN in the range of 20 to 80 μM increased lipid peroxidation in a concentration-dependent manner from about 15% to about 50%. Kynurenic acid, a compound metabollically related to QUIN that can block its neurotoxic actions in vivo, also inhibited completely the QUIN-induced TBA-RP formation in our system. Lipid fluorescent material, another index of lipid peroxidation was also found increased by 49% after incubation with 40 μM QUIN. It is concluded that lipid peroxidation may be a damaging process involved in the neurotoxicity of QUIN.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bruyn, R. P. M., and Stoof, J. C. 1990. The quinolinic acid hypothesis in Huntington's chorea. J. Neurol. Sci. 95:29–38.

    PubMed  Google Scholar 

  2. Heyes, M. P., Wyler, A. R., Devinsky, O., Yergey, J. A., Markey, S. P., and Nadi, S. 1990. Quinolinic acid concentrations in brain and cerebrospinal fluid of patients with intractable complex partial seizures. Epilepsia. 31:172–177.

    PubMed  Google Scholar 

  3. Feldblum, S., Rougier, A., Loiseau, H., Loiseau, P., Cohadon, F., Morselli, P. L., and Lloyd, K. G. 1988. Quinolinic-phosphoribosyl transferase activity is decreased in epileptic human brain tissue. Epilepsia. 29:523–529.

    PubMed  Google Scholar 

  4. Beal, M. F., Kowall, N. W., Ellison, D. W., Mazurek, M. F., Swartz, K. J., and Martin, J. B. 1986. Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid. Nature 321:168–171.

    PubMed  Google Scholar 

  5. Lapin, I. P. 1981. Kynurenines and seizures. Epilepsia 22:257–265.

    PubMed  Google Scholar 

  6. Perkins, M. N., and Stone, T. W. 1983. Pharmacology and regional variations of quinolinic acid-evoked excitations in the rat central nervous system. J. Pharmacol. Exp. Ther. 226:551–557.

    PubMed  Google Scholar 

  7. Moroni, F., Lombardi, G., Carla, V., Pellegrini, D., Corassale, G., and Cortessini, C. 1986. Content of quinolinic acid and of other triptophan metabolites increases in brain regions of rats used as experimentals models of hepatic encephalopathy. J. Neurochem. 46:869–874.

    PubMed  Google Scholar 

  8. Schwarcz, R., Foster, A. C., French, E. D., Whetsell, Jr., N. O., and Kohler, C. 1984. Excitotoxic models for neurodegenerative disorders. Life Sciences 35:19–32.

    PubMed  Google Scholar 

  9. Choi, D. W. 1988. Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage. Trends Neurosci. 11:465–469.

    PubMed  Google Scholar 

  10. Foster, A. C., Collins, J. F., and Schwarcz, R. 1983. On the excitotoxic properties of quinolinic acid, 2,3-piperidine dicarboxylic acid and structurally related compounds. Neuropharmacol. 22:1331–1342.

    Google Scholar 

  11. Halliwell, B., and Gutteridge, M. C. 1984. Oxygen toxicity oxygen radicals, transition metals and disease. Biochem. J. 219:1–14.

    PubMed  Google Scholar 

  12. Zaleska, M. A., and Floyd, R. A. 1985. Regional lipid peroxidation in rat brain in vitro: possible role of endogenous iron. Neurochem. Res. 10:397–410.

    PubMed  Google Scholar 

  13. Kogure, K. B. D., Watson, B., Busto, R., and Abe, K. 1982. Potentiation of lipid peroxides by ischemia in rat brain. Neurochem. Res. 7:437–454.

    PubMed  Google Scholar 

  14. Calabrese, V., and Fariello, R. G. 1988. Regional distribution of malondialdehyde in mouse brain. Biochem. Pharmacol. 37:2287–2288.

    PubMed  Google Scholar 

  15. Willmore, L. J., and Rubin, J. J. 1981. Antiperoxidant pretreatment and iron-induced epileptiform discharges in the rat: EEG and histopathologic studies. Neurology 31:63–69.

    PubMed  Google Scholar 

  16. Fong, T. M., and McNamme, G. M. 1986. Correlation between acetylcholine receptor function and structural properties of membranes. Biochemistry. 25:830–840.

    PubMed  Google Scholar 

  17. Braughler, J. M. 1985. Lipid peroxidation-induced inhibition of gamma-aminobutiric acid uptake in rat brain synaptosomes: protection by gluco-corticoids. J. Neurochem. 44:1282–1288.

    PubMed  Google Scholar 

  18. Singh, R., and Pathak, D. N. 1990. Lipid peroxidation and glutathione reductase, superoxide dismutase, catalase and glucose-6-phosphate dehydrogenase activities in FeCl3-induced epileptogenic foci in the rat brain. Epilepsia 31:15–26.

    PubMed  Google Scholar 

  19. Wilbur, K. M., Bernheim, F., and Shapiro, O. W. 1949. The thiobarbituric acid reagent as a test for the oxidation of unsaturated fatty acids by various agents. Arch. Biochem. Biophys. 24:305–313.

    Google Scholar 

  20. Waravdekar, V. S., and Saslaw, L. D. 1959. A sensitive colorimetric method for the estimation of 2-deoxy-sugars with the use of the malonaldehyde-thiobarbituric acid reaction. J. Biol. Chem. 234:1945–1950.

    PubMed  Google Scholar 

  21. Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. 1951. Protein measurement with the Folin-phenol reagent. J. Biol. Chem. 193:265–275.

    PubMed  Google Scholar 

  22. Triggs, W. J., and Willmore, L. J. 1984. In vivo lipid peroxidation in rat brain following intracortical Fe++ injection. J. Neurochem. 42:976–979.

    PubMed  Google Scholar 

  23. Calza, L., Giardino, L., Velardo, A., Battistini, N., and Marrama, P. 1990. Iron-dependent peroxidation of rat brain: a regional study. J. Neurosci. Res. 26:224–232.

    PubMed  Google Scholar 

  24. Steel, R. G. D., and Torrie, J. H. 1980. Principles and procedures of statistics. 2nd edition. McGraw-Hill.

  25. Rehncrona, S., Smith, D. S., Akeson, B., Westergerd, E., and Siesjo, B. K. 1980. Peroxidative changes in brain cortical fatty acids and phospholipids as characterized during Fe++ and ascorbic acid stimulated lipid peroxidation in vitro. J. Neurochem. 34:1630–1638.

    PubMed  Google Scholar 

  26. Chan, P. H., Yurko, M., and Fishman, R. A. 1982. Phospholipid degradation and cellular edema induced by free radicals in brain cortical slices. J. Neurochem. 38:525–531.

    PubMed  Google Scholar 

  27. Garthwaite, G., and Garthwaite, J. 1987. Quinolinate mimics neurotoxic actions of the N-methyl-d-aspartate in rat cerebellar slices. Neurosci. Lett. 79:35–39.

    PubMed  Google Scholar 

  28. Whetsell, W. O. 1984. The use of organotypic tissue culture for the study of aminoacid neurotoxicity and its antagonism in the mammalian CNS. Clin. Neuropharmacol. 7:238–250.

    Google Scholar 

  29. Sztriha, L. 1986. Increased lipid peroxide formation in the rat forebrain during kainic acid seizures. Biomed. Biochem. Acta. 45:491–494.

    Google Scholar 

  30. Foster, A. C., Vezzani, A., French, E. D., and Schwarcz, R. 1984. Kynutrenic acid blocks neurotoxicity and seizures induced in rats by the related brain metabolite quinolinic acid. Neurosci. Lett. 48:273–278.

    PubMed  Google Scholar 

  31. Crawford, M., Roberts, P. J. 1989. 1-hydroxy-3-aminopyrrolid-2-one (HA 966) and kynureninate antagonize N-methyl-D-aspartate induced enchancement of 3H-dopamine release from rat striatal slices. Biochem. Pharmacol. 38:4165–4168.

    PubMed  Google Scholar 

  32. Pullan, L. M., and Cler, J. A. 1989. Schild plot analysis of glycine and kynurenic acid at the N-methyl-D-aspartate excitatory amino acid receptor. Brain Res. 497:59–63.

    PubMed  Google Scholar 

  33. Bors, W., Buettner, G. R., Michel, C., and Saran, M. 1990. Calcium in lipid peroxidation: Does calcium interact with superoxide? Arch. Biochem. Biophys. 278:269–272.

    PubMed  Google Scholar 

  34. Tsuzuki, K., Iino, M., Ozawa, S. 1989. Change in calcium permeability caused by quinolinic acid in cultured rat hippocampal neurons. Neurosci. Lett. 105:269–274.

    PubMed  Google Scholar 

  35. Halliwell, B., and Gutteridge, M. C. 1985. Free radicals in biology and medicine. Oxford-Claredon.

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rios, C., Santamaria, A. Quinolinic acid is a potent lipid peroxidant in rat brain homogenates. Neurochem Res 16, 1139–1143 (1991). https://doi.org/10.1007/BF00966592

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00966592

Key Words

Navigation