Zhong Wang, Qiuhan Wang, Xuezhong Gong
Arsenic is a toxic element that is widely present in both natural and clinical environments, posing a significant threat to human health. Long-term exposure to arsenic may lead to multiorgan damage, with the kidneys, as the primary target organs for arsenic metabolism and excretion, being particularly vulnerable to its toxic effects. Increasing evidence suggests that arsenic exposure is associated with the occurrence of acute kidney injury and the progression of chronic kidney disease. Previous studies have primarily focused on mechanisms such as oxidative stress, mitochondrial dysfunction, and programmed cell death. However, these mechanisms do not fully explain the complexity of arsenic nephrotoxicity. In this review, we systematically review recent advancements in the understanding of arsenic-induced renal injury, with a particular focus on novel mechanisms, including epigenetic regulation, noncoding RNA-mediated gene expression regulation, and metabolic reprogramming, as revealed by omics techniques. These new mechanisms provide a theoretical foundation for enhancing our understanding of arsenic nephrotoxicity, discovering potential biomarkers, and developing targeted intervention strategies. Additionally, we assess the effectiveness and limitations of current management approaches, such as chelation therapy, antioxidant applications, and supportive treatments. It is worth noting that a growing body of evidence suggests that traditional Chinese medicine might offer renal protection through antioxidant, anti-inflammatory, and immunomodulatory pathways. Our previous studies have also demonstrated that the Chuanhuang formula and its active ingredient, tetramethylpyrazine, could effectively alleviate arsenic-induced acute kidney injury. Finally, we hope to mitigate the potential health risks posed by arsenic exposure through multidisciplinary collaboration and comprehensive intervention.