Swimming Into View: Zebrafish Uncover Targets, Mechanisms, and Therapies for Cadmium Toxicity

Purpose: of Review Cadmium (Cd) remains a persistent threat to human and environmental health. To better understand causal relationships between genotype and disease phenotypes, a genetically tractable model, zebrafish (Danio rerio) has emerged. We summarize recent empirical evidence on the targets, mechanisms, and potential therapies for Cd toxicity. Recent Findings Recent results show that waterborne Cd exhibits organ specific accumulation including in the eye, brain, heart, and gonads triggering oxidative stress, inflammation, gut dysbiosis, and altered methylation patterns that persist across generations. Novel mechanisms of Cd toxicity include the gut-brain axis, ionic antagonism, Wnt/β-catenin pathway, and epigenetics, leading to potential therapeutics such as probiotics, selenium, antioxidants. Summary Based on the reviewed literature, more studies should examine the effects of dietary Cd on zebrafish behavior, brains, and cardiovascular function. Given that humans and wildlife are chronically exposed to Cd, leading to gonadal Cd accumulation, studies should conduct early-life exposures across the zebrafish lifespan and assess endpoints across generations to capture germline and epigenetic effects and mechanisms. The zebrafish's biomedical toolkit, along with high-content screening, should be utilized to develop and refine therapies.