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

摘要

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.