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

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

doi:10.1007/s12640-017-9863-1

ORIGINAL ARTICLE
Published: 08 January 2018

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

Marisol Maya-López¹,
María Verónica Mireles-García^1,2^na1,
Monserrat Ramírez-Toledo^1,3^na1,
Ana Laura Colín-González¹,
Sonia Galván-Arzate⁴,
Isaac Túnez⁵ &
Abel Santamaría¹

Neurotoxicity Research volume 33, pages 634–640 (2018)Cite this article

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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.).

Author information

María Verónica Mireles-García and Monserrat Ramírez-Toledo contributed equally to this work.

Authors and Affiliations

Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía, Insurgentes Sur 3877, 14269, Mexico City, Mexico
Marisol Maya-López, María Verónica Mireles-García, Monserrat Ramírez-Toledo, Ana Laura Colín-González & Abel Santamaría
Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, 44100, Tlaquepaque, Jalisco, Mexico
María Verónica Mireles-García
Escuela Superior de Medicina, Instituto Politécnico Nacional, 07738, Mexico City, Mexico
Monserrat Ramírez-Toledo
Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía, 14269, Mexico City, Mexico
Sonia Galván-Arzate
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina y Enfermería, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba, 14004, Córdoba, Spain
Isaac Túnez

Authors

Marisol Maya-López
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María Verónica Mireles-García
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Monserrat Ramírez-Toledo
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Ana Laura Colín-González
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Sonia Galván-Arzate
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Isaac Túnez
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Abel Santamaría
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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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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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Received: 22 November 2017
Revised: 25 December 2017
Accepted: 28 December 2017
Published: 08 January 2018
Issue Date: April 2018
DOI: https://doi.org/10.1007/s12640-017-9863-1

Keywords

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