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. 2010 May;115(1):194-201.
doi: 10.1093/toxsci/kfq036. Epub 2010 Feb 4.

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

Daiana S Avila  1 , 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
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A possible neuroprotective action of a vinylic telluride against Mn-induced neurotoxicity

Daiana S Avila et al. Toxicol Sci. 2010 May.

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 long-term 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 MnCl(2) (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 micromol/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 [(3)H]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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Figures

FIG. 1.
FIG. 1.
Neurobehavioral evaluation in rats exposed to Mn for 4 months (13.7 mg/kg) and cotreated for 14 days with DPTVP (0.150 μmol/kg). (A) Number of crossings in the open field, (B) number of rearing in the open field, and (C) latency for the first fall in the rotarod. Each bar represents mean ± SEM (n = 5 each group); ns, nonsignificant statistical significance.
FIG. 2.
FIG. 2.
Effects of the Mn exposure (13.7 mg/kg) and/or cotreatment with DPTVP (0.150 μmol/kg) on TBARS levels in cortex (A), hippocampus (B), and striatum (C) of treated rats. Data are expressed as nanomoles of malondialdehyde per milligram of protein. Each bar represents mean ± SEM (n = 5). *Indicates statistical difference from control group.
FIG. 3.
FIG. 3.
Mitochondrial viability in cortex (A), hippocampus (B), and striatum (C) of animals chronically exposed to Mn and cotreated for 14 days with DPTVP. Data are expressed as percentage of control (100% values are 0.87 delta of absorbance per milligram of protein for cortex, 0.58 delta of absorbance per milligram of protein for hippocampus, and 0.59 delta of absorbance per milligram of protein for straitum). Each bar represents mean ± SEM (n = 5). *Indicates statistical difference from control group.
FIG. 4.
FIG. 4.
[3H]glutamate uptake in cortex (A), hippocampus (B), and striatum (C) of animals chronically exposed to Mn and cotreated for 14 days with DPTVP. Data are expressed as nanomoles of [3H]glutamate per milligrams of protein per minute. Each bar represents mean ± SEM (n = 5). *Indicates statistical difference from control group.
FIG. 5.
FIG. 5.
Mn levels in rat striatum after chronic Mn exposure and/or cotreatment with DPTVP. Data are expressed as micrograms of Mn per gram of wet tissue. Each bar represents mean ± SEM (n = 5). *Indicates statistical difference from control group.
FIG. 6.
FIG. 6.
Schematic representation of Mn neurotoxicity. Mn is selectively deposited in striatum, causing oxidative stress, glutamate homeostasis deregulation, and mitochondrial impairment. These alterations can feed each other in a vicious cycle that will culminate in behavioral changes (motor impairment).
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