Cadmium-induced neurotoxicity: still much ado

Abstract

Cadmium (Cd) is a highly toxic heavy metal that accumulates in living system and as such is currently one of the most important occupational and environmental pollutants. Cd reaches into the environment by anthropogenic mobilization and it is absorbed from tobacco consumption or ingestion of contaminated substances. Its extremely long biological half-life (approximately 20-30 years in humans) and low rate of excretion from the body cause cadmium storage predominantly in soft tissues (primarily, liver and kidneys) with a diversity of toxic effects such as nephrotoxicity, hepatotoxicity, endocrine and reproductive toxicities. Moreover, a Cd-dependent neurotoxicity has been also related to neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, and multiple sclerosis. At the cellular level, Cd affects cell proliferation, differentiation, apoptosis and other cellular activities. Among all these mechanisms, the Cd-dependent interference in DNA repair mechanisms as well as the generation of reactive oxygen species, seem to be the most important causes of its cellular toxicity. Nevertheless, there is still much to find out about its mechanisms of action and ways to reduce health risks. This article gives a brief review of the relevant mechanisms that it would be worth investigating in order to deep inside cadmium toxicity.

Keywords: 17β-estradiol; G-protein-coupled estrogen receptor-30; blood-brain barrier permeability; cadmium; metallothionein; neurodegenerative disorders; oxidative stress; reactive oxygen species; toxicity.

Figure 1

Schematic representation of selected cadmium (Cd)-related cellular pathways and nuclear interactions. AT: Active ATPase transporter; PC: passive channel or carrier; GPCR: G-protein-coupled estrogen receptor-30 (GPR30); G: G-protein; MT: metallothionein; GSH: glutathione; GPx: Glutathione peroxidase; ROS: reactive oxygen species; ER: endoplasmic reticulum.