Heavy metals (Pb,Cd, As and MeHg) as risk factors for cognitive dysfunction: A general review of metal mixture mechanism in brain |
| |
| Institution: | 1. Division of Clinical Pharmacology and Pediatric Toxicology, Vanderbilt University Medical Center, Nashville, TN, USA;2. The Kennedy Center for Research on Human Development, Vanderbilt University Medical Center, Nashville, TN, USA;3. Center in Molecular Toxicology, Vanderbilt University Medical Center, Nashville, TN, USA;4. Center for Molecular Neuroscience, Vanderbilt University Medical Center, Nashville, TN, USA;1. Institute for Psychology, Sigmund Freud University Linz, Linz, Austria;2. University Department of Physical Medicine, Rehabilitation and Occupational Medicine, Medical University of Vienna, Vienna, Austria;3. Leibniz-Institute for Educational Trajectories, Bamberg, Germany;4. Institute of Education and Psychology, Johannes Keppler University Linz, Linz, Austria;5. IGGMB-Health Research Institute, University Clinics of the Paracelsus Medical University, Salzburg, Austria;6. Health and Prevention Center of the Insurance Institution for the Vienna Employee, Vienna, Austria |
| |
| Abstract: | Human exposure to toxic heavy metals is a global challenge. Concurrent exposure of heavy metals, such as lead (Pb), cadmium (Cd), arsenic (As) and methylmercury (MeHg) are particularly important due to their long lasting effects on the brain. The exact toxicological mechanisms invoked by exposure to mixtures of the metals Pb, Cd, As and MeHg are still unclear, however they share many common pathways for causing cognitive dysfunction. The combination of metals may produce additive/synergetic effects due to their common binding affinity with NMDA receptor (Pb, As, MeHg), Na+ ? K+ ATP-ase pump (Cd, MeHg), biological Ca+2 (Pb, Cd, MeHg), Glu neurotransmitter (Pb, MeHg), which can lead to imbalance between the pro-oxidant elements (ROS) and the antioxidants (reducing elements). In this process, ROS dominates the antioxidants factors such as GPx, GS, GSH, MT-III, Catalase, SOD, BDNF, and CERB, and finally leads to cognitive dysfunction. The present review illustrates an account of the current knowledge about the individual metal induced cognitive dysfunction mechanisms and analyse common Mode of Actions (MOAs) of quaternary metal mixture (Pb, Cd, As, MeHg). This review aims to help advancement in mixture toxicology and development of next generation predictive model (such as PBPK/PD) combining both kinetic and dynamic interactions of metals. |
| |
| Keywords: | Metal toxicity Metal mixture Cognitive dysfunction Hippocampus Mode of actions |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
