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Antioxidant Properties of New Chalcogenides Against Lipid Peroxidation in Rat Brain

Neurochemical Research volume 27, pages 297–303 (2002)Cite this article

Abstract

Ebselen (2-phenyl- 1,2-benzisoselenazole-3 (2H)-one) is a seleno-organic compound with antioxidant properties, and anti-inflammatory actions. Recently, ebselen improved the outcome of acute ischemic stroke in humans. In the present study, the potential antioxidant capacity of organochalcogenide compounds diphenyl diselenide (PhSe)2, diphenyl ditelluride (PhTe)2, diphenyl disulfide (PhS)2, p-Cl-diphenyl diselenide (pCl-PhSe)2, bis-[S-4-isopropyl 2-phenyl oxazoline] diselenide (AA-Se)2, bis-[S-4-isopropyl 2-phenyl oxazoline] ditelluride (AA-Te)2 and bis-[S-4-isopropyl 2-phenyl oxazoline] disulfide (AA-S)2 was compared with that of ebselen (a classical antioxidant). Spontaneous and quinolinic acid (QA)- (2 mM) and sodium nitroprusside (SNP)- (5 μM)-induced thiobarbituric reactive species (TBARS) production by rat brain homogenates was determined colorimetrically. TBARS formation was reduced by ebselen, (PhSe)2, (PhTe)2, (AA-Se)2, (AA-S)2 and (pCl- PhSe)2 to basal rates. The concentrations of these compounds needed to inhibit TBARS formation by 50% (lC50) are 1.71 μM, 3.73 μM, 1.63 μM, 9.85 μM, > 33.3 μM, 23.2 μM and 4.83 μM, respectively for QA. For TBARS production induced by SNP the lC50 was 2.02 μM, 12.5 μM, 2.80 μM, > 33.3 μM, 24.5 μM and 7.55 μM, respectively. The compounds (AA-Te)2 and (PhS)2 have no antioxidant activity and pro-oxidant activity, respectively. These results suggest that (AA-Se)2 and (AA-S)2 can be considered as potential pharmaceutical antioxidant agents.

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REFERENCES

  1. Dawson, V. L. and Dawson, T. M. 1996. Free radicals and neuronal cell death. Death and Differentiation 3:71–76.

    Google Scholar 

  2. Siesjo, B., Agardh, C. D., and Bengtsson, F. 1989. Free radicals and brain damage. Cerebrovasc. Brain Metab. Rev. 1:165–211.

    Google Scholar 

  3. Taystman, R. J., Kirsch, J. R., and Koehler, R. C. 1991. Oxygen radical mechanisms of brain injury following ischaemia and reperfusion. J. Appl. Physiol. 71:1185–1995.

    Google Scholar 

  4. Schwarcz, R., Whetsell, W. O. Jr., and Mangano, R. M. 1983. Quinolinic acid: an endogenous metabolite that produces axonsparing lesions in rat brain. Science 219:316–318.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  7. Tsuzuki, K., Lino, M., and Ozawa, S. 1989. Change in calcium permeability caused by quinolinic acid in cultured rat hippocampal neurones. Neuroscience Letters 15:269–274.

    Google Scholar 

  8. Maclamon, J. G. and Curry, K. 1990. Quinolinate activation of N-methyl-D-aspartate ion channels in rat hippocampal neurons. Neuroscience Letters 116:341–346.

    Google Scholar 

  9. Daniel, L. C. 1991. N-methyl-D-aspartate increases cytoplasmic free calcium in mouse hippocampus. Neuropharmacology 30:539–545.

    Google Scholar 

  10. Gutteridge, J. M. C. 1977. The effect of calcium on phospholipid peroxidation. Biochem. Biophys. Res. Comm. 74:529–537.

    Google Scholar 

  11. Babiszhayev, M. A. 1988. The biphasic effects of calcium on lipid peroxidation. Arch. Biochem. Biophys. 266:446–451.

    Google Scholar 

  12. Keilhoff, G., Wolf, G., Stastny, F., and Schmidt, W. 1990. Quinolinate neurotoxicity and glutamatergic structures. Neuroscience 34:235–242.

    Google Scholar 

  13. Arnold, W. P., Longneeker, D. E., and Epstein, R. M. 1984. Photodegradation of sodium nitroprusside: Biologic activity and cyanide release. Anesthesiology 61:254–260.

    Google Scholar 

  14. Bates, J. N., Baker, M. T., Guerra, R., and Harrison, D. G. 1990. Nitric oxide generation from nitroprusside by vascular tissue. Biochem. Pharmacol. 42:S157–S165.

    Google Scholar 

  15. Smith, R. P. and Kruszyna, H. 1974. Nitroprusside produces cyanide poisoning via a reaction with hemoglobin. J. Pharmacol. Exp. Ther. 191:557–563.

    Google Scholar 

  16. Mortensen, E. 1964. The nitroprusside method for the determination of reduced glutathione. Scand. J. Clin. Lab. Invest. 1:87–97.

    Google Scholar 

  17. Rauhala, P., Kmaldi, A., Mohanakumar, K. P., and Chiueh, C. C. 1998. Apparent role of hydroxyl radicals in oxidative brain injury induced by sodium nitroprusside. Free radical Biology & Medicine 24:1065–1073.

    Google Scholar 

  18. Maiorino, M., Roveri, A., Coassin, M., and Ursini, F. 1988. Kinetic mechanism and substrate specificity of glutathione peroxidase activity of ebselen (PZ51). Biochem. Pharmacol. 37:2267–2271.

    Google Scholar 

  19. Müller, A., Cadenas, E., Graf, P., and Sies, H. 1984. A novel biologically active seleno-organic compound I. Glutathione peroxidase-like activity in vitro and antioxidant capacity of PZ51 (Ebselen). Biochem. Pharmacol. 33:3235–3239.

    Google Scholar 

  20. Malecki, A., Garrido, R., Mattson, M. P., Henning, B., and Toborek, M. 2000. 4–Hydroxynonenal induces oxidative stress and death of cultured spinal cord neurons. J. Neurochem. 74:2278–2287.

    Google Scholar 

  21. Takasago, T., Peters, E. E., Graham, D. I., Masayasu, H., and Macrae, I. M. 1997. Neuroprotective efficacy of ebselen, an antioxidant with antiinflammatory actions, in a rodent model of permanent middle cerebral artery oclusion. Br. J. Pharmacol. 122:1251–1256.

    Google Scholar 

  22. Yamaguchi, T., Sano, K., Takakura, K., Saito, I., Shinohara, Y., Asano, T., and Yasuhara, H. 1998. Ebselen in acute ischaemic stroke: a placebo-controlled, double-blind clinical trial. Stroke 29:12–17.

    Google Scholar 

  23. PorciÚncula, L. O., Rocha, J. B. T., Boeck, C. R., Vendite, D., and Souza, D. O. 2001. Ebselen prevents excitotoxicity provoked by glutamate in rat cerebellar granule neurons. Neuroscience Letters 299:217–220.

    Google Scholar 

  24. Saito, I., Asano, T., Sano, K., Takakura, K., Abe, H., Yoshimoto, T., Kikichi, H., Ohta, T., and Ishibashi, S. 1998. Neuroprotective effect of an antioxidant, ebselen, in patients with delayed neurological deficits after aneurysmal subarachnoid hemorrhage. Neurosurgery 42:269–278.

    Google Scholar 

  25. Herin, G. A., Du, S., and Aizenman, E. 2001. The neuroprotective ebselen modifies NMDA receptor function via the redox modulatory site. J. Neurochem. 78:1307–1314.

    Google Scholar 

  26. Anderson, C. M., Hallberg, A., Brattsand, R., Cotgreave, I. A., Engman, L., and Person, J. 1993. Glutathione peroxidase-like activity of diaryl tellurides. Bioorganic & Medicinal Chemistry Letters 3:2553–2558.

    Google Scholar 

  27. Anderson, C. M., Brattsand, R., Hallberg, A. R., Engman, L., Persson, J., Moldéus, P., and Cotgreave, I. 1994. Diaryl tellurides as inhibitors of lipid peroxidation in biological and chemical systems. Free Radic. Res. 20:401–410.

    Google Scholar 

  28. Nogueira, C. W., Maciel, E. N., Zeni, G., Graça, D., and Rocha, J. B. T. 2001. Biochemical toxicology of simple diorganyl chalcogenides. ECSOC, http://www.mdpi.net/ecsoc-5/, [d0013].

  29. Santamaria, A, Santamaria, D., Diaz-Munoz, M., Espinoza-Gonzalez, V., and Rios, C. 1997. Effects of N omega-nitro-L-arginine and L-arginine on quinolinic acid-induced lipid peroxidation. Toxicology Letters, 93:117–124.

    Google Scholar 

  30. Ohkawa, H., Ohishi, N., and Yagi, K. 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 95:351–358.

    Google Scholar 

  31. Engman, L. 1989. Expedient synthesis of ebselen and related componds. J. Org. Chem. 54:2964–2966.

    Google Scholar 

  32. Petragnani, N. 1994. Tellurium in organic synthesis. San Diego: Academic Press, 248p.

    Google Scholar 

  33. Paulmier, C. 1986. Selenium reagents and intermediates in organic synthesis. New York: Pergamon Press, 463p.

    Google Scholar 

  34. Braga, A. L., Silva, S. N., Marchi, M. I., Sehnem, J. A., and Lüdtke, D. S. 2000. Nova metodologia de obtenção de fosfinas/dissulfetos oxazolínicos quirais. 23° Reunião Anual da SBQ/QO-121.

  35. Braga, A. L., Wessjohann, L. A., Silveira, C. C., Scheineder, P. H., Drekener, R. L., and S. J. N. 2001. Chiral diselenides ligands for the asymmetric copper catalyzed conjugate addition of grignard reagents to enones. 9th Brazilian meeting on organic synthesis-BMOS/PS-161.

  36. Dixon, M. and Webb, E. C. 1964. Enzymes, 2nd Ed, Longmans, London and Colchester, 950p.

    Google Scholar 

  37. Miranda, A. F., Sutton, M. A., Beninger, R. J., Jhamandas, K., and Boegman, R. J. 1999. Quinolinic acid lesions of the nigrostriatal pathway: effect on turning behavior and protection by elevation of endogenous kynurenic acid in Rattus norvegicus. Neuroscience Letters 262:81–84.

    Google Scholar 

  38. Rodrígez-Martínez, E., Camacho, A., Maldonado, P. D., Pedraza-Chaverri, J., Santamaría, D., Galván-Arzate, S., and Santamaria, A. 2000. Effect of quinolinic acid on endogenous antioxidant in rat corpus striatum. Brain Research 858:436–439.

    Google Scholar 

  39. Santamaría, A. and Ríos, C. 1993. MK-801, an N-methyl-D-aspartate receptor antagonist, blocks quinolinic acid-induced lipid peroxidation in rat corpus striatum. Neuroscience Letters 159:51–54.

    Google Scholar 

  40. Yamada, M., Momose, K., Richelson, E., and Yamada, M. 1996. Sodium nitroprusside-induced apoptotic cellular death via production of hydrogen peroxide in murine neuroblastoma NIE-115 cells. J. Pharmacol. Toxicol. Methods 35:11–17.

    Google Scholar 

  41. Graf, E., Mahoney, J. R., Bryant, R. G., and Eaton, J. W. 1984. Iron-catalyzed hydroxyl radical formation: Stringent requirement for free iron coordination site. J. Biol. Chem. 259:3620–3624.

    Google Scholar 

  42. Haliwell, B. 1992. Reactive oxygen species and the central nervous system. J. Neurochem. 59:1609–1623.

    Google Scholar 

  43. Mohanakumar, K. P., De Bartolomeis, A., Wu, R.-M., Yeh, K. J., Stenmberger, L. M., Peng, S. Y., Murphy, D. L., and Chiueh, C. C. 1994. Ferrous-citrate complex and degeneration: Evidence for free-radical formation and lipid peroxidation. Ann. N. Y. Acad. Sci. 738:392–399.

    Google Scholar 

  44. Rossato, J. I., Zeni, G., Mello, F. C., Rubin, M. A., and Rocha, J. B. T. 2002. Ebselen blocks the quinolinic acid-induced production of thiobarbituric acid reactive species but does not prevent the behavioral alterations produced by intra-striatal quinolinic acid administration in the rat. Neuroscience Letters. 318:137–140.

    Google Scholar 

  45. Engman, L., Person, J., Vessman, K., Ekstron, M., Berglund, M., and Andersson, C. M. 1995. Organotellurium compounds as efficient retarders of lipid peroxidation in methanol. Free Radical Biology & Medicine 19:441–452.

    Google Scholar 

  46. Nogueira, C. W., Rotta, L. N., Perry, M. L., Souza, D. O., and da Rocha, J. B. T. 2001. Diphenyl diselenide and diphenyl ditelluride affect the rat glutamatergic system in vitro and in vivo. Brain Research 906:157–163.

    Google Scholar 

  47. Maciel, E. N., Bolzan, R. C., Braga, A. L., and Rocha, J. B. T. 2000. Diphenyl diselenide and diphenyl diteluride differentially affect aminolevulinate dehydratase from liver, kidney and brain of mice. J. Biochem. Mol. Toxicol. 14:310–319.

    Google Scholar 

  48. Nogueira, C. W., Quinhones, E. B., Jung, E. A. C., Zeni, G*., Rocha, J. B. T. Evidence for anti-inflammatory and antinociceptive activity of diphenyl diselenide. Submitted.

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Authors and Affiliations

  1. Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brasil

    J. I. Rossato, L. A. Ketzer, F. B. Centurião, S. J. N. Silva, D. S. Lüdtke, G. Zeni, A. L. Braga, M. A. Rubin & J. B. T. Rocha

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Rossato, J.I., Ketzer, L.A., Centurião, F.B. et al. Antioxidant Properties of New Chalcogenides Against Lipid Peroxidation in Rat Brain. Neurochem Res 27, 297–303 (2002). https://doi.org/10.1023/A:1014907228580

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  • DOI: https://doi.org/10.1023/A:1014907228580

  • Antioxidants
  • organochalcogenides
  • lipid peroxidation
  • quinolinic acid
  • sodium nitroprusside