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Diphenyl diselenide and diphenyl ditelluride: neurotoxic effect in brain of young rats, in vitro

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Abstract

This study examined whether maturity of rat brain may be relevant for the sensitivity to diphenyl diselenide (PhSe)2 and diphenyl ditelluride (PhTe)2 on [3H]glutamate uptake and release, in vitro. Brain synaptosomes were isolated from young (14- and 30-day-old) and adult rats and incubated at different concentrations of (PhSe)2 or (PhTe)2. The results demonstrated that the highest concentration (100 μM) of (PhSe)2 and (PhTe)2 inhibited the [3H]glutamate uptake by synaptosomes of brain at all ages. In the adult brain, (PhSe)2 did not inhibit the [3H]glutamate uptake at the lowest concentration (10 μM). The highest concentration of (PhTe)2 inhibited the [3H]glutamate uptake more in the 14-day-old than in the 30-day-old rats or adult rats. In the 30-day-old animals, the highest concentration of (PhSe)2, and the lowest concentration of (PhTe)2, increased the basal [3H]glutamate release. At the highest concentration, (PhTe)2 increased the basal and K+-stimulated glutamate release on all ages evaluated. The results suggest that (PhSe)2 and (PhTe)2 caused alterations on the homeostasis of the glutamatergic system at the pre-synaptic level. These alterations were age-, concentration-, and compound-dependent. The maturity of rat brain is relevant for the glutamatergic system sensitivity to (PhSe)2 and (PhTe)2 .

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References

  1. Ozawa S, Kamiya H, Tsukuki K (1998) Glutamate receptors in the mammalian central nervous system. Progr Neurobiol 54:581–618

    Article  CAS  Google Scholar 

  2. Longuemare MC, Swanson RA (1995) Excitatory amino acid release from astrocytes during energy failure by reversal of sodium-dependent uptake. J Neurosci Res 40:379–386

    Article  CAS  PubMed  Google Scholar 

  3. Bock A, Forchammer JH, Leinfelder W, Sawers G, Vepreck B, Zinnia F (1991) Selenocysteine: the 21st amino acid. Mol Microbiol 5:515–520

    Article  CAS  PubMed  Google Scholar 

  4. Parnham M, Sies H (2000) Ebselen: prospective therapy for cerebral ischaemia. Expert Opin Invest Drug 9:607–619

    Article  CAS  Google Scholar 

  5. Schroeder HA, Buckman J, Balassa JJ (1967) Abnormal trace elements in man: tellurium. J Chronic Dis 20:147–161

    Article  CAS  PubMed  Google Scholar 

  6. Taylor A (1996) Biochemistry of tellurium. Biol Trace Elem Res 55:231–239

    Article  CAS  PubMed  Google Scholar 

  7. Meotti FC, Stangherlin EC, Zeni G, Nogueira CW, Rocha JBT (2004) Protective role of aryl and alkyl diselenides on lipid peroxidation. Environ Res 94:276–282

    Article  CAS  PubMed  Google Scholar 

  8. Nogueira CW, Zeni G, Rocha JBT (2004) Organoselenium and organotellurium compounds: toxicology and pharmacology. Chem Rev 104:6255–6285

    Article  CAS  PubMed  Google Scholar 

  9. Prigol M, Schumacher RF, Nogueira CW, Zeni G (2009) Convulsant effect of diphenyl diselenide in rats and mice and its relationship to plasma levels. Toxicol Lett 189:35–39

    Article  CAS  PubMed  Google Scholar 

  10. Nogueira CW, Quinhones EB, Jung EAC, Zeni G, Rocha JBT (2003) Evidence for anti-inflammatory and antinociceptive activity for diphenyl diselenide. Inflamm Res 52:56–63

    Article  CAS  PubMed  Google Scholar 

  11. Savegnago L, Trevisan M, Alves D, Rocha JBT, Nogueira CW, Zeni G (2006) Antisecretory and antiulcer effects of diphenyl diselenide. Environ Toxicol Pharmacol 21:86–92

    Article  CAS  Google Scholar 

  12. Acker CI, Luchese C, Prigol M, Nogueira CW (2009) Antidepressant-like effect of diphenyl diselenide on rats exposed to malathion: involvement of Na+K+ATPase activity. Neurosci Lett 455:168–172

    Article  CAS  PubMed  Google Scholar 

  13. Stangherlin EC, Luchese C, Ardais AP, Nogueira CW (2009) Passive smoke exposure induces oxidative damage in brains of rat pups: Protective role of diphenyl diselenide. Inhal Toxicol 21:868–874

    Article  CAS  PubMed  Google Scholar 

  14. Prigol M, Wilhelm EA, Schneider CC, Rocha JBT, Nogueira CW, Zeni G (2007) Involvement of oxidative stress in seizures induced by diphenyl diselenide in rat pups. Brain Res 1147:226–232

    Article  CAS  PubMed  Google Scholar 

  15. Prigol M, Wilhelm EA, Stangherlin EC, Barancelli DA, Nogueira CW, Zeni G (2008) Diphenyl diselenide-induced seizures in rat pups: possible interaction with glutamatergic system. Neurochem Res 33:996–1004

    Article  CAS  PubMed  Google Scholar 

  16. Stangherlin EC, Favero AM, Zeni G, Rocha JBT, Nogueira CW (2005) Teratogenic vulnerability of Wistar rats to diphenyl ditelluride. Toxicology 207:231–239

    Article  CAS  PubMed  Google Scholar 

  17. Stangherlin EC, Favero AM, Zeni G, Rocha JBT, Nogueira CW (2006) Exposure of mothers to diphenyl ditelluride during the suckling period changes behavioral tendencies in their offspring. Brain Res Bull 69:311–317

    Article  CAS  PubMed  Google Scholar 

  18. Stangherlin EC, Ardais AP, Rocha JBT, Nogueira CW (2009) Exposure to diphenyl ditelluride, via maternal milk, causes oxidative stress in cerebral cortex, hippocampus and striatum of young rats. Arch Toxicol 83:485–491

    Article  CAS  PubMed  Google Scholar 

  19. Stangherlin EC, Rocha JBT, Nogueira CW (2009) Diphenyl ditelluride impairs short-term memory and alters neurochemical parameters in young rats. Pharmacol Biochem Behav 91:430–435

    Article  CAS  PubMed  Google Scholar 

  20. Nogueira CW, Rotta LN, Perry ML, Souza DO, Rocha JBT (2001) Diphenyl diselenide and diphenyl ditelluride affect the rat glutamatergic system in vitro and in vivo. Brain Res 906:157–163

    Article  CAS  PubMed  Google Scholar 

  21. Nogueira CW, Rotta LN, Zeni G, Souza DO, Rocha JBT (2002) Exposure to ebselen changes glutamate uptake and release by rat brain synaptosomes. Neurochem Res 27:283–288

    Article  CAS  PubMed  Google Scholar 

  22. Paulmier C (1986) Selenium reagents and intermediates in organic synthesis, 1st edn. Pergamon press, Oxford

    Google Scholar 

  23. Petragnani N (1994) Preparation of the principal classes of organic tellurium compounds. In: Katritzky AR, Meth-Cohn O, Rees CW (eds) Tellurium in organic synthesis. Academic Press, London, pp 9–88

    Google Scholar 

  24. Dunkley PR, Heath J, Harrison SM, Jarvie PE, Glenfield PY, Rostas JAP (1988) A rapid gradient procedure for isolation of synaptosomes directly from an S-1 fraction-homogeneity and morphology of subcellular fractions. Brain Res 441:59–71

    Article  CAS  PubMed  Google Scholar 

  25. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  26. Migues PV, Leal RB, Mantovani M, Nicolau M, Gabilan NH (1999) Synaptosomal glutamate release induced by the fraction Bc2 from the venon of the sea anemone Bunodosoma caissarum. Neuroreport 10:67–70

    Article  CAS  PubMed  Google Scholar 

  27. Robinson MB, Dowd LA (1997) Heterogeneity and functional subtypes of sodium-dependent glutamate transporters in the mammalian central nervous system. Adv Pharmacol 37:69–115

    Article  CAS  PubMed  Google Scholar 

  28. Fykse EM, Fonnum F (1996) Amino acid neurotransmission: dynamics of vesicular uptake. Neurochem Res 21:1053–1060

    Article  CAS  PubMed  Google Scholar 

  29. Danbolt NC (1994) The high affinity uptake system for excitatory amino acids in the brain. Progr Neurobiol 44:377–396

    Article  CAS  Google Scholar 

  30. Wolosker H, Reis M, Assreuy J, de Meis L (1996) Inhibition of glutamate uptake and proton pumping in synaptic vesicles by S-nitrosylation. J Neurochem 66:1943–1948

    Article  CAS  PubMed  Google Scholar 

  31. Moretto MB, Rossato JI, Nogueira CW, Zeni G, Rocha JBT (2003) Voltage-dependent ebselen and diorganochalcogenides inhibition of Ca-45(2+) influx into brain synaptosomes. J Biochem Mol Toxicol 17:154–160

    Article  CAS  PubMed  Google Scholar 

  32. Maciel EN, Bolzan RC, Braga AL, Rocha JBT (2000) Diphenyl diselenide and diphenyl ditelluride differentially affect d-Aminolevulinate dehydratase from liver, kidney, and brain of mice. J Biochem Mol Toxicol 14:310–319

    Article  CAS  PubMed  Google Scholar 

  33. Götz ME, Künig G, Riederer P, Youdim MBH (1994) Oxidative stress: free radical production in neural degeneration. Pharmacol Ther 63:37–122

    Article  PubMed  Google Scholar 

  34. Patel M, Day BJ, Crapo JD, Fridovich I, McNamara JO (1996) Requirement for superoxide in excitotoxic cell death. Neuron 16:345–355

    Article  CAS  PubMed  Google Scholar 

  35. Coyle JT, Puttfarchen P (1993) Oxidative stress, glutamate, and neurodegenerative disorders. Science 26:689–695

    Article  Google Scholar 

  36. Borges VC, Rocha JB, Nogueira CW (2005) Effect of diphenyl diselenide, diphenyl ditelluride and ebselen on cerebral Na(+), K(+)-ATPase activity in rats. Toxicology 215:191–197

    Article  CAS  PubMed  Google Scholar 

  37. Beal MF, Hyman BT, Koroshetz W (1993) Do defects in mitochondrial energy metabolism underlie the pathology of neurodegenerative diseases. Trends Neurosci 16:125–131

    Article  CAS  PubMed  Google Scholar 

  38. Nogueira CW, Meotti FC, Curte E, Pilissão C, Zeni G, Rocha JBT (2003) Investigations into the potential neurotoxicity induced by diselenides in mice and rats. Toxicology 183:29–37

    Article  CAS  PubMed  Google Scholar 

  39. Perez-D’Gregorio RE, Miller RK (1988) Teratogenicity of tellurium dioxide: prenatal assessment. Teratology 37:307–316

    Article  PubMed  Google Scholar 

  40. Muller R, Zschiesche W, Steffen HM, Schaller KH (1989) Tellurium-intoxication. Klin Wochenschr 67:1152–1155

    Article  CAS  PubMed  Google Scholar 

  41. Spiller HA, Pfiefer E (2007) Two fatal cases of selenium toxicity. Forensic Sci Int 171:67–72

    Article  CAS  PubMed  Google Scholar 

  42. Morgane JP, Mokler JD, Galler RJ (2002) Effets of prenatal protein malnutrition on the hipocampal formation. Neurosci Biobehav Rev 26:471–483

    Article  CAS  PubMed  Google Scholar 

  43. Wolff JR, Balcar VJ, Zetzsche T, Böttcher H, Schmechel DE, Chronwall BM (1984) Development of GABA-ergic system in rat visual cortex. Adv Exp Med Biol 181:215–239

    CAS  PubMed  Google Scholar 

  44. Olney JW (1980) Excitatory neurotoxins as food additives: an evaluation of risk. Neurotoxicology 2:153–192

    Google Scholar 

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Acknowledgments

The financial support by FAPERGS, CAPES, and CNPq is gratefully acknowledged. C. W. N. is the recipient of CNPq fellowship.

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Authors and Affiliations

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

    Ana Cristina Guerra Souza, Eluza Curte Stangherlin, Ana Paula Ardais & Cristina Wayne Nogueira

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  1. Ana Cristina Guerra Souza
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  2. Eluza Curte Stangherlin
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  3. Ana Paula Ardais
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  4. Cristina Wayne Nogueira
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Correspondence to Cristina Wayne Nogueira.

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Souza, A.C.G., Stangherlin, E.C., Ardais, A.P. et al. Diphenyl diselenide and diphenyl ditelluride: neurotoxic effect in brain of young rats, in vitro. Mol Cell Biochem 340, 179–185 (2010). https://doi.org/10.1007/s11010-010-0416-7

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  • DOI: https://doi.org/10.1007/s11010-010-0416-7

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