Thallium-Induced Toxicity in Rat Brain Crude Synaptosomal/Mitochondrial Fractions is Sensitive to Anti-excitatory and Antioxidant Agents.
Neurotox Res
; 33(3): 634-640, 2018 04.
Article
em En
| MEDLINE
| ID: mdl-29313218
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sinaptossomos
/
Tálio
/
Encéfalo
/
Mitocôndrias
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article