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Neurotoxicity Research

, Volume 33, Issue 3, pp 634–640 | Cite as

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

  • Marisol Maya-López
  • María Verónica Mireles-García
  • Monserrat Ramírez-Toledo
  • Ana Laura Colín-González
  • Sonia Galván-Arzate
  • Isaac Túnez
  • Abel Santamaría
ORIGINAL ARTICLE

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.

Keywords

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

Notes

Funding Information

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

Compliance with Ethical Standards

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.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018
corrected publication January/2018

Authors and Affiliations

  • Marisol Maya-López
    • 1
  • María Verónica Mireles-García
    • 1
    • 2
  • Monserrat Ramírez-Toledo
    • 1
    • 3
  • Ana Laura Colín-González
    • 1
  • Sonia Galván-Arzate
    • 4
  • Isaac Túnez
    • 5
  • Abel Santamaría
    • 1
  1. 1.Laboratorio de Aminoácidos ExcitadoresInstituto Nacional de Neurología y NeurocirugíaMexico CityMexico
  2. 2.Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de GuadalajaraTlaquepaqueMexico
  3. 3.Escuela Superior de MedicinaInstituto Politécnico NacionalMexico CityMexico
  4. 4.Departamento de NeuroquímicaInstituto Nacional de Neurología y NeurocirugíaMexico CityMexico
  5. 5.Departamento de Bioquímica y Biología Molecular, Facultad de Medicina y Enfermería, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)Universidad de CórdobaCórdobaSpain

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