Exposure of humans to heavy metals such as lead (Pb) and cadmium (Cd) has been significantly increased due to the industrial activities of the past century and causes global health concerns. Pb and Cd can encounter humans through both dietary and environmental pathways. Despite extensive research on individual metals, the integrated mechanisms of mixed Pb-Cd exposure remain poorly understood, especially under chronic low-dose conditions representative of a real-world scenario. Hence, the present review focuses on the acute effects of Pb and Cd on human disease, intracellular dynamics, their distinct toxicity pathways, and their detection techniques. While Pb interferes with calcium-dependent signaling and mitochondrial function via impersonation of Ca2+ and altered redox homeostasis, Cd preferably displaces Zn2+ from metalloproteins, associates intracellularly with metallothionein and, consequently, induces long-lasting oxidative and endoplasmic reticulum stress. Toxicity pathways for both metals converge toward key nodes of cellular dysfunction, including overproduction of reactive oxygen species, disturbance in the MAPK/NF-κB cascade, and impaired DNA repair. Further, in addition to apoptosis, heavy metals disrupt cellular processes such as proliferation, differentiation, growth, and damage repair. The study further contextualizes the molecular perturbations within the food chain as an exposure vector, showing how staple foods like cereals, vegetables, and seafood uniformly contribute to cumulative Pb and Cd intake across populations. This integrated exposure-toxicity paradigm underlines growing risks associated with chronic, low-dose, mixed-metal exposure. Despite the current understanding of the toxicology of heavy metals, their prevalence is still significant and necessitates a regulatory framework.
Mazumder et al. (2026) studied this question.