A possible neuroprotective action of a vinylic telluride against Mn-induced neurotoxicity

Daiana S. Ávila, Dirleise Colle, Priscila Gubert, Aline S. Palma, Gustavo Puntel, Flávia Manarin, Simone Noremberg, Paulo C. Nascimento, Michael Aschner, João B T Rocha, Félix A A Soares

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Manganese (Mn) is a metal required by biological systems. However, environmental or occupational exposure to high levels of Mn can produce a neurological disorder called manganism, which has similarities to Parkinson's disease. Diethyl-2-phenyl-2-tellurophenyl vinylphosphonate (DPTVP) is an organotellurium compound with a high antioxidant activity, especially in the brain. The present study was designed to investigate the effects of longterm low-dose exposure to Mn in drinking water on behavioral and biochemical parameters in rats and to determine the effectiveness of vinylic telluride in attenuating the effects of Mn. After 4 months of treatment with MnCl2 (13.7 mg/kg), rats exhibited clear signs of neurobehavioral toxicity, including a decrease in the number of rearings in the open field and altered motor performance in rotarod. The administration of DPTVP (0.150 μmol/kg, ip, 2 weeks) improved the motor performance of Mn-treated rats, indicating that the compound could be reverting Mn neurotoxicity. Ex vivo, we observed that Mn concentrations in the Mn-treated group were highest in the striatum, consistent with a statistically significant decrease in mitochondrial viability and [3H]glutamate uptake, and increased lipid peroxidation. Mn levels in the hippocampus and cortex were indistinguishable from controls, and no significant differences were noted in the ex vivo assays in these areas. Treatment with DPTVP fully reversed the biochemical parameters altered by Mn. Furthermore, DPTVP treatment was also associated with a reduction in striatal Mn levels. Our results demonstrate that DPTVP has neuroprotective activity against Mn-induced neurotoxicity, which may be attributed to its antioxidant activity and/or its effect on striatal Mn transport.

Original languageEnglish (US)
Pages (from-to)194-201
Number of pages8
JournalToxicological Sciences
Volume115
Issue number1
DOIs
StatePublished - May 2010
Externally publishedYes

Fingerprint

Manganese
Corpus Striatum
Rats
Antioxidants
Environmental Exposure
Biological systems
Occupational Exposure
Nervous System Diseases
Drinking Water
Lipid Peroxidation
Parkinson Disease
Toxicity
Glutamic Acid
Assays
Hippocampus
Brain
Metals
diethyl 2-phenyl-2 tellurophenyl vinylphosphonate

Keywords

  • Glutamate
  • Manganese neurotoxicity
  • Mitochondria
  • Neuroprotector
  • Oxidative stress
  • Tellurium

ASJC Scopus subject areas

  • Toxicology
  • Medicine(all)

Cite this

Ávila, D. S., Colle, D., Gubert, P., Palma, A. S., Puntel, G., Manarin, F., ... Soares, F. A. A. (2010). A possible neuroprotective action of a vinylic telluride against Mn-induced neurotoxicity. Toxicological Sciences, 115(1), 194-201. https://doi.org/10.1093/toxsci/kfq036

A possible neuroprotective action of a vinylic telluride against Mn-induced neurotoxicity. / Ávila, Daiana S.; Colle, Dirleise; Gubert, Priscila; Palma, Aline S.; Puntel, Gustavo; Manarin, Flávia; Noremberg, Simone; Nascimento, Paulo C.; Aschner, Michael; Rocha, João B T; Soares, Félix A A.

In: Toxicological Sciences, Vol. 115, No. 1, 05.2010, p. 194-201.

Research output: Contribution to journalArticle

Ávila, DS, Colle, D, Gubert, P, Palma, AS, Puntel, G, Manarin, F, Noremberg, S, Nascimento, PC, Aschner, M, Rocha, JBT & Soares, FAA 2010, 'A possible neuroprotective action of a vinylic telluride against Mn-induced neurotoxicity', Toxicological Sciences, vol. 115, no. 1, pp. 194-201. https://doi.org/10.1093/toxsci/kfq036
Ávila, Daiana S. ; Colle, Dirleise ; Gubert, Priscila ; Palma, Aline S. ; Puntel, Gustavo ; Manarin, Flávia ; Noremberg, Simone ; Nascimento, Paulo C. ; Aschner, Michael ; Rocha, João B T ; Soares, Félix A A. / A possible neuroprotective action of a vinylic telluride against Mn-induced neurotoxicity. In: Toxicological Sciences. 2010 ; Vol. 115, No. 1. pp. 194-201.
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abstract = "Manganese (Mn) is a metal required by biological systems. However, environmental or occupational exposure to high levels of Mn can produce a neurological disorder called manganism, which has similarities to Parkinson's disease. Diethyl-2-phenyl-2-tellurophenyl vinylphosphonate (DPTVP) is an organotellurium compound with a high antioxidant activity, especially in the brain. The present study was designed to investigate the effects of longterm low-dose exposure to Mn in drinking water on behavioral and biochemical parameters in rats and to determine the effectiveness of vinylic telluride in attenuating the effects of Mn. After 4 months of treatment with MnCl2 (13.7 mg/kg), rats exhibited clear signs of neurobehavioral toxicity, including a decrease in the number of rearings in the open field and altered motor performance in rotarod. The administration of DPTVP (0.150 μmol/kg, ip, 2 weeks) improved the motor performance of Mn-treated rats, indicating that the compound could be reverting Mn neurotoxicity. Ex vivo, we observed that Mn concentrations in the Mn-treated group were highest in the striatum, consistent with a statistically significant decrease in mitochondrial viability and [3H]glutamate uptake, and increased lipid peroxidation. Mn levels in the hippocampus and cortex were indistinguishable from controls, and no significant differences were noted in the ex vivo assays in these areas. Treatment with DPTVP fully reversed the biochemical parameters altered by Mn. Furthermore, DPTVP treatment was also associated with a reduction in striatal Mn levels. Our results demonstrate that DPTVP has neuroprotective activity against Mn-induced neurotoxicity, which may be attributed to its antioxidant activity and/or its effect on striatal Mn transport.",
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