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.

Characteristics of selected bioaccumulative substances and their impact on fish health

“…It contributes to an increase in reactive oxygen species (ROS) formation. Successively, ROS may lead to damage of enzymes, nucleic acids, and lipids, and may lead to cell death (43).…”

“…Toxicity of lead in the environment depends on its various forms. Organolead compounds, which are mainly made of covalent bonds, exhibit toxicological effects different from inorganic lead salts (43). Lead causes damage to living systems by releasing free radicals.…”

“…Lead causes damage to living systems by releasing free radicals. They may increase directly by generation of ROS such as O2, H2O2, or indirectly through the depletion of antioxidants in cells (43). Lead exerts toxic effects through its ability to inhibit or mimic the actions of calcium and to interact with proteins.…”

“…Moreover, it binds to sulfhydryl and amide groups of enzymes, altering their configuration and diminishing their activities. For example, lead causes inhibition of δ-aminolevulinic acid dehydratase (ALAD) (41,43). Interaction of lead and ALAD results in enhancement of ROS formation (41).…”

“…The formed complex is released back into the circulation. Proximal tubular cells of the kidneys absorb the Cd-metallothionein complex (22,43). This form of cadmium causes hepatotoxicity in the liver, and may circulate to kidneys leading to nephrotoxicity (22).…”