Heavy Metal Havoc: Deciphering the Cellular Mechanisms of Cadmium Toxicity

Abstract

Cadmium (Cd), a ubiquitous heavy metal pollutant, poses a significant threat to human health and the environment. The primary contributors to Cd pollution include drinking water, tainted food products, cigarette smoking, mineral extraction and processing, industrial applications, and the widespread utilization of Cd batteries. Cd enters cells primarily through passive diffusion and active transport mechanisms involving divalent metal transporters (DMTs). Once inside the cell, Cd accumulates in various sub-cellular compartments, including the cytoplasm, endoplasmic reticulum (ER), mitochondria, and nucleus. The way Cd is distributed within cells holds significant importance in influencing the harmful effects of Cd exposure. Cd-triggered toxicity primarily stems from oxidative stress, due to the formation of oxygen and nitrogen derived free radicals such H2O2, HO•, O2•−, RO•, ROO•, NO•, NO2• and ROO•. This oxidative stress can result in lipid peroxidation, damage to proteins, and fragmentations and alterations in DNA strands, thereby contributing to cellular dysfunction and the process of apoptosis. Cd can also modulate various signalling pathways, including MAPKs, NF-κB, JNK and p53, further exacerbating cellular damage.