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Metabolic Brain Disease

, Volume 15, Issue 4, pp 249–256 | Cite as

An Investigation into the Neuroprotective Properties of Ibuprofen

  • Zaynab Lambat
  • Natasha Conrad
  • Shailendra Anoopkumar-Dukie
  • Roderick B. Walker
  • Santy Daya
Article

Abstract

There is increasing evidence suggesting a protective role for anti-inflammatory medications in neurological disorders such as Alzheimer's disease (AD). While there has not been any direct evidence for this, a number of clinical studies indicate that those patients who have had a history of nonsteroidal anti-inflammatory use, have a lower incidence of AD. Since there is currently no evidence on the mechanism by which these agents offer possible neuroprotection, we investigated the potential neuroprotective properties of the nonsteroidal anti-inflammatory drug, ibuprofen, by examining whether this agent could reduce lipid peroxidation and superoxide radical generation. Quinolinic acid and cyanide, known neurotoxins, were used to induce lipid peroxidation and superoxide anion formation respectively, in rat brain homogenate. The results show that ibuprofen significantly (p<0.05) reduced quinolinic acid-induced lipid peroxidation and cyanide-induced superoxide production. The results of the present report therefore suggest a possible mechanism for the neuroprotective effect of ibuprofen.

Ibuprofen neurodegeneration free radical 

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REFERENCES

  1. Agid, Y. (1991). Parkinsons disease:pathophysiology. Lancet 337:1321-1327.Google Scholar
  2. Anoopkumar-Dukie, S., Walker, R.B., and Daya, S. A sensitive and reliable method for the detection of lipid peroxidation in biological tissues. J. Pharm. Pharmacol. (In Press).Google Scholar
  3. Anthony, J.C., Breitner, J.C.S., Zandi, P.P., Meyer, M.R., Jurasova, I., Norton, M.C., and Stone, S.V. (2000). Reduced prevalence of AD in users of NSAIDS and H2 receptor antagonists. Neurology 54:2066-2071.Google Scholar
  4. Ardelt, B.K., Borowitz, J.L., and Isom, G.E. (1994). Brain lipid peroxidation and antioxidant protectant mechanisms following acute cyanide intoxication. Toxicology 56:147-154.Google Scholar
  5. Broe, G.A., Henderson, A.S., Creasey, H., McCusker, E., Korten, A.E., Jorm, A.F., Longley, W., and Anthony, J.C. (1990). A case-control study of Alzheimer's disease in Australia. Neurology 40:1698-1707.Google Scholar
  6. Coyle, J., and Puttfarken P. (1993). Oxidative stress, glutamate and neurodegenerative disorders. Science 262:689-695.Google Scholar
  7. Daya, S. (1999). The role of melatonin as a neuroprotectant in Alzheimer's disease. Spec. Med. 31:528-537.Google Scholar
  8. Halliwell, B. (1992). Reactive oxygen species and the central nervous system. J. Neurochem. 59:1609-1623.Google Scholar
  9. Henry, D., Lim, L.L.Y., Rodriguez, L.A.G., Gutthann, S.P., Carson, J.L., Griffin, M., Savage, R., Logan, R., Moride, Y., Hawkey, C., Hill, S. and Fries, J.T. (1996). Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis. BMJ 312:1563-1566.Google Scholar
  10. Heyes, M.P., Achim, C.L., Wiley, C.A., Major, E.O., Saito, K., and Markey, S.P. (1996). Human microglia convert L-tryptophan to the neurotoxin quinolinic acid. Biochem. J. 320:595.Google Scholar
  11. Johnson, J.D., Conroy, W.G., Burris, K.D., and Isom, G.E. (1987). Peroxidation of brain lipids following cyanide intoxication in mice. Toxicology 46:21-28.Google Scholar
  12. 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.Google Scholar
  13. McGeer, P.L., Akiyama, H., Itagaki, S., and McGeer, E.G. (1989). Immune system response in Alzheimer's disease. Can. J. Neurol. Sci. 16:516-527.Google Scholar
  14. Moroni, F., Lombard, G., Moneti, G., and Aldino, C. (1984). The excitotoxin quinolinic acid is present in the brain of several mammals and its cortical content increases during the aging process. Neurosci. Lett. 47:51.Google Scholar
  15. Ottino, P., and Duncan, J.R. (1997). Effect of α-tocopherol succinate on free radical and lipid peroxidation levels in BL6 melanoma cells. Free Radic. Biol. Med. 22:1145-1151.Google Scholar
  16. Rich, J.B., Rasmusson, D.X., Folstein, M.F., Carson, K.A., Kawas, C., and Brandt, J. (1995). Nonsteroidal anti-inflammatory drugs in Alzheimer's disease. Neurology 45:51-54.Google Scholar
  17. Saano, V., Paronen, P., Peura, P., and Vidgren, M. (1991). Relative pharmacokinetics of three oral 400mg ibuprofen dosage forms in healthy volunteers. Int. J. Clin. Pharmacol.Ther. Toxicol. 29:381-385.Google Scholar
  18. Shaw, P.J. (1994). Excitotoxicity and motor neurone disease: a review of the evidence. J. Neurol. Sci. 124:6-13.Google Scholar
  19. Southgate, G., and Daya, S. (1999). Melatonin reduces Quinolinic acid-induced Lipid peroxidation in rat brain homogenate. Met. Brain Dis. 14:165-171.Google Scholar
  20. Steinberg, M. (2000). Pharmacological treatment of Alzheimer's disease: an update on approved, unapproved therapies. Modern Medicine 38:47.Google Scholar
  21. Stone, T.W. and Perkins, M.N. (1981). Quinolinic acid: A potent endogenous excitant at amino acid receptors in CNS. Eur. J. Pharmacol 72:411-412.Google Scholar
  22. Stone, T.W.(1993). Neuropharmacology of quinolinic acid and kynurenic acid. Pharmacol. Rev. 48:309.Google Scholar
  23. Wolfensberger, M., Amsler, U., Cuenod, M., Foster, A.C. et al., (1983). Identification of quinolinic acid in rat and human brain tissue. Neurosci. Lett. 41:247-252.Google Scholar
  24. Zar, J. H. (1974). Biostatistical analysis. Englewood Cliffs, NJ: Prentice Hall, 151-466.Google Scholar

Copyright information

© Plenum Publishing Corporation 2000

Authors and Affiliations

  • Zaynab Lambat
    • 1
  • Natasha Conrad
    • 1
  • Shailendra Anoopkumar-Dukie
    • 1
  • Roderick B. Walker
    • 1
  • Santy Daya
    • 2
  1. 1.Faculty of PharmacyRhodes UniversityGrahamstownSouth Africa
  2. 2.Faculty of PharmacyRhodes UniversityGrahamstownSouth Africa

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