title: A review of toxicity and mechanisms of individual and mixtures of heavy metals in the environment.
abstract: The rational for the study was to review the literature on the toxicity and corresponding mechanisms associated with lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (As), individually and as mixtures, in the environment. Heavy metals are ubiquitous and generally persist in the environment, enabling them to biomagnify in the food chain. Living systems most often interact with a cocktail of heavy metals in the environment. Heavy metal exposure to biological systems may lead to oxidation stress which may induce DNA damage, protein modification, lipid peroxidation, and others. In this review, the major mechanism associated with toxicities of individual metals was the generation of reactive oxygen species (ROS). Additionally, toxicities were expressed through depletion of glutathione and bonding to sulfhydryl groups of proteins. Interestingly, a metal like Pb becomes toxic to organisms through the depletion of antioxidants while Cd indirectly generates ROS by its ability to replace iron and copper. ROS generated through exposure to arsenic were associated with many modes of action, and heavy metal mixtures were found to have varied effects on organisms. Many models based on concentration addition (CA) and independent action (IA) have been introduced to help predict toxicities and mechanisms associated with metal mixtures. An integrated model which combines CA and IA was further proposed for evaluating toxicities of non-interactive mixtures. In cases where there are molecular interactions, the toxicogenomic approach was used to predict toxicities. The high-throughput toxicogenomics combines studies in genetics, genome-scale expression, cell and tissue expression, metabolite profiling, and bioinformatics.
authors.affiliation: School of the Environment, Jiangsu University, Xuefu Rd. 301, Zhenjiang, 212013, Jiangsu, China. wuxy@ujs.edu.cn.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Wu
authors.affiliation: School of the Environment, Jiangsu University, Xuefu Rd. 301, Zhenjiang, 212013, Jiangsu, China.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Cobbina
authors.affiliation: School of the Environment, Jiangsu University, Xuefu Rd. 301, Zhenjiang, 212013, Jiangsu, China.
authors.forename: Guanghua
authors.initials: G
authors.lastname: Mao
authors.affiliation: School of the Environment, Jiangsu University, Xuefu Rd. 301, Zhenjiang, 212013, Jiangsu, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Xu
authors.affiliation: School of the Environment, Jiangsu University, Xuefu Rd. 301, Zhenjiang, 212013, Jiangsu, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Chemistry and Chemical Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang, 212013, China. yangliuqing@ujs.edu.cn.
authors.forename: Liuqing
authors.initials: L
authors.lastname: Yang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001151:Arsenic; D002104:Cadmium / Q000633:toxicity; D004249:DNA Damage / Q000187:drug effects; D004777:Environment; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity*; D015227:Lipid Peroxidation; D008628:Mercury / Q000633:toxicity; D008670:Metals / Q000378:metabolism; D019216:Metals, Heavy / Q000378:metabolism / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004785:Environmental Pollutants; D008670:Metals; D019216:Metals, Heavy; D017382:Reactive Oxygen Species; D002104:Cadmium; D008628:Mercury; D001151:Arsenic
keywords: Low dose; Metal mixtures; Mode of action; Oxidative stress; Toxicogenomics