Biochemical Mechanisms of Heavy Metal-Induced Oxidative Stress in Humans; Article Review

Toxic metals are still a very important biochemical and public health issue because certain metals like lead (Pb), cadmium (Cd), mercury (Hg) and arsenic (As) can be found in environmental media, and disrupt the homeostasis of cells. Oxidative stress is one of the key pathways but not exclusive pathway of toxicity caused by metals. Metals can cause an increase in the production of Reactive Oxygen Species (ROS), damage mitochondria, interact with sulfhydryl groups, disrupt the homeostasis of the essential metals, and cause changes in antioxidant signaling. These modifications can lead to the initiation of lipid peroxidation, protein oxidation, DNA damage, inflammation and cell-death signaling. This review is a summary of biochemical pathways associated with metal-induced oxidative injury, the nature of commonly used biomarkers (malondialdehyde [MDA], glutathione [GSH], superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx] and 8-hydroxy-2′-deoxyguanosine [8-OHdG]), and the difficulties in using biomarkers to inform clinical or environmental-health decisions. Specificity of assays, sample handling, exposure assessment, confounding, and distinguishing between mechanistic plausible and proven clinical causation are highlighted. The available evidence reviewed shows that it is more beneficial to use a group of validated exposure measurements along with a panel of biochemical markers than on a single oxidative stress indicator. More standardization of analytical protocols, longitudinal study designs and better integration of environmental and biological measurements are needed for better comparability and clinical interpretation.