Okutsu Jessica, Noor Md Imran, Shelton Delia S
Department of Biology, University of Miami, 1301 Memorial Dr., Cox Science Building Rm 27, Coral Gables, FL, 33146, USA.
Curr Environ Health Rep. 2025 Apr 22;12(1):20. doi: 10.1007/s40572-025-00471-0.
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 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, the Wnt/β-catenin pathway, and epigenetics, leading to potential therapeutics such as probiotics, selenium, and antioxidants. 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.
镉(Cd)仍然是对人类和环境健康的持续威胁。为了更好地理解基因型与疾病表型之间的因果关系,一种具有遗传易处理性的模型——斑马鱼(Danio rerio)应运而生。我们总结了关于镉毒性的靶点、机制和潜在治疗方法的最新实验证据。
最近的结果表明,水体中的镉在包括眼睛、大脑、心脏和性腺在内的器官中表现出特异性积累,引发氧化应激、炎症、肠道微生物群失调以及跨代持续存在的甲基化模式改变。镉毒性的新机制包括肠-脑轴、离子拮抗、Wnt/β-连环蛋白途径和表观遗传学,从而产生了如益生菌、硒和抗氧化剂等潜在治疗方法。基于综述文献,更多研究应考察膳食镉对斑马鱼行为、大脑和心血管功能的影响。鉴于人类和野生动物长期接触镉会导致性腺镉积累,研究应在斑马鱼的整个生命周期进行早期暴露,并评估跨代终点,以捕捉种系和表观遗传效应及机制。应利用斑马鱼的生物医学工具包以及高内涵筛选来开发和完善治疗方法。