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.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2ElLrzx