Neurotoxicity of Metals

Laura Osorio-Rico, Abel Santamaria, Sonia Galván-Arzate

Thallium (Tl(+)) is a ubiquitous natural trace metal considered as the most toxic among heavy metals. The ionic ratio of Tl(+) is similar to that of potassium (K(+)), therefore accounting for the replacement of the latter during enzymatic reactions. The principal organelle damaged after Tl(+) exposure is mitochondria. Studies on the mechanisms of Tl(+) include intrinsic pathways altered and changes in antiapoptotic and proapoptotic proteins, cytochrome c, and caspases. Oxidative damage pathways increase after Tl(+) exposure to produce reactive oxygen species (ROS), changes in physical properties of the cell membrane caused by lipid peroxidation, and concomitant activation of antioxidant mechanisms. These processes are likely to account for the neurotoxic effects of the metal. In humans, Tl(+) is absorbed through the skin and mucous membranes and then is widely distributed throughout the body to be accumulated in bones, renal medulla, liver, and the Central Nervous System. Given the growing relevance of Tl(+) intoxication, in recent years there is a notorious increase in the number of reports attending Tl(+) pollution in different countries. In this sense, the neurological symptoms produced by Tl(+) and its neurotoxic effects are gaining attention as they represent a serious health problem all over the world. Through this review, we present an update to general information about Tl(+) toxicity, making emphasis on some recent data about Tl(+) neurotoxicity, as a field requiring attention at the clinical and preclinical levels.