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Thallium-Induced Toxicity in Rat Brain Crude Synaptosomal/Mitochondrial Fractions is Sensitive to Anti-excitatory and Antioxidant Agents

Abstract

The mechanisms by which the heavy metal thallium (Tl+) produces toxicity in the brain remain unclear. Herein, isolated synaptosomal/mitochondrial P2 crude fractions from adult rat brains were exposed to Tl+ (5–250 μM) for 30 min. Three toxic endpoints were evaluated: mitochondrial dysfunction, lipid peroxidation, and Na+/K+-ATPase activity inhibition. Concentration-response curves for two of these endpoints revealed the optimum concentration of Tl+ to induce damage in this preparation, 5 μM. Toxic markers were also estimated in preconditioned synaptosomes incubated in the presence of the N-methyl-d-aspartate receptor antagonist kynurenic acid (KYNA, 50 μM), the cannabinoid receptor agonist WIN 55,212-2 (1 μM), or the antioxidant S-allyl-L-cysteine (SAC, 100 μM). All these agents prevented Tl+ toxicity, though SAC did it with lower efficacy. Our results suggest that energy depletion, oxidative damage, and Na+/K+-ATPase activity inhibition account for the toxic pattern elicited by Tl+ in nerve terminals. In addition, the efficacy of the drugs employed against Tl+ toxicity supports an active role of excitatory/cannabinoid and oxidative components in the toxic pattern elicited by the metal.

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Funding

This work was supported by CONACyT Grant 205648 (A.S.).

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Correspondence to Abel Santamaría.

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All experiments were carried out following the criteria stated in the “Guidelines for the Use of Animals in Neuroscience Research” from the Society of Neuroscience, the local Bioethics Committees, and in compliance with the ARRIVE guidelines.

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The authors declare that they have no conflict of interest.

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Maya-López, M., Mireles-García, M.V., Ramírez-Toledo, M. et al. Thallium-Induced Toxicity in Rat Brain Crude Synaptosomal/Mitochondrial Fractions is Sensitive to Anti-excitatory and Antioxidant Agents. Neurotox Res 33, 634–640 (2018). https://doi.org/10.1007/s12640-017-9863-1

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  • DOI: https://doi.org/10.1007/s12640-017-9863-1

Keywords

  • Thallium
  • Mitochondrial reductant capacity
  • Oxidative stress
  • Na+/K+-ATPase activity
  • Neurotoxicity
  • Brain synaptosomes