Heavy metals (Pb, Cd, As and MeHg) as risk factors for cognitive dysfunction: A general review of metal mixture mechanism in brain.
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.
Center of Environmental Food and Toxicological Technology (TecnATox), Departament d'Enginyeria Química, Universitat Rovira i Virgili, Tarragona, Catalonia, Spain.
Venkatanaidu
V
Karri
Center of Environmental Food and Toxicological Technology (TecnATox), Departament d'Enginyeria Química, Universitat Rovira i Virgili, Tarragona, Catalonia, Spain.
Marta
M
Schuhmacher
Center of Environmental Food and Toxicological Technology (TecnATox), Departament d'Enginyeria Química, Universitat Rovira i Virgili, Tarragona, Catalonia, Spain. Electronic address: vikas.kumar@urv.cat.
Vikas
V
Kumar
D000818:Animals; D001151:Arsenic / Q000493:pharmacokinetics / Q000633:toxicity; D001667:Binding, Competitive; D002104:Cadmium / Q000493:pharmacokinetics / Q000633:toxicity; D002118:Calcium / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000139:chemically induced* / Q000378:metabolism; D045424:Complex Mixtures / Q000493:pharmacokinetics / Q000633:toxicity*; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D018698:Glutamic Acid / Q000378:metabolism; D020260:Heavy Metal Poisoning, Nervous System / Q000209:etiology* / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007854:Lead / Q000493:pharmacokinetics / Q000633:toxicity; D019216:Metals, Heavy / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000493:pharmacokinetics / Q000633:toxicity; D008954:Models, Biological; D011485:Protein Binding; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012307:Risk Factors; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D045424:Complex Mixtures; D004785:Environmental Pollutants; D019216:Metals, Heavy; D008767:Methylmercury Compounds; D016194:Receptors, N-Methyl-D-Aspartate; D002104:Cadmium; D007854:Lead; D018698:Glutamic Acid; D000254:Sodium-Potassium-Exchanging ATPase; D001151:Arsenic; D002118:Calcium
Cognitive dysfunction; Hippocampus; Metal mixture; Metal toxicity; Mode of actions