Molecular mechanisms of cadmium toxicity in mammals

Cadmium (Cd) is a toxic metal, targeting several organs, such as lungs, liver, kidneys, and testes, following acute intoxication. It produces nephrotoxicity, immunotoxicity, osteotoxicity, cardiotoxicity and tumors in human beings and other mammals, after prolonged exposures. Different organisms, organs and/or tissues vary in their susceptibility to cadmium. These differences are determined by numerous factors, including Cd preferred intracellular accumulation in nucleus or cytoplasm and the cellular capacity to induce the synthesis of protective factors, like metallothioneines and glutathione. The mechanisms of cadmium citotoxicity involve: interaction with nucleic acids, producing DNA damage; increase of oxidative stress; substitution of zinc ions in –SH groups of proteins; substitution of calcium ions; and interaction with enzymes and proteins, disturbing the activities of diverse enzymes including antioxidant enzymes and DNA repair enzymes. Cd has also been reported to bind and deplete reduced glutathione (GSH) within the cell. Thus, cadmium cellular damage leads to cell death, including necrosis and apoptosis, as well as to an increased expression of several oncogenes. The present review focuses on the effects of cadmium in mammalian cells, comparing the most relevant mechanisms of its toxicity accordingly with the cellular type under study.Fil: Larregle, Ethel Viviana. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Bioquímica y Ciencias Biológicas; ArgentinaFil: Ferramola, Mariana Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentin