Department of Biotechnology, Jinan University, Guangzhou, Guangdong Province, China.
Department of Chemistry, Tsinghua University, Beijing, China.
Redox Biol. 2022 Jun;52:102321. doi: 10.1016/j.redox.2022.102321. Epub 2022 Apr 25.
Arsenic (As) contamination in drinking water is a global public health problem. Epidemiological studies have shown that selenium (Se) deficiency is associated with an increasing risk of arsenism. However, the association between Se status and As retention in erythrocytes and mechanisms underlying this association have not been fully investigated. In the present study, a total of 165 eligible subjects were recruited and As was found to accumulate in blood mainly by retention in erythrocytes. Retention of As in erythrocytes was negatively correlated with Se status, antioxidant parameters related to Se and As methylation capacity, but positively correlated with the protein-binding capacity of As. Additionally, erythrocytes isolated from subjects with low Se status exhibited cellular damage along with lower protein levels of CD47, which could be aggravated by hydrogen peroxide treatment. Consistent with the human study, the erythrocytes from mice with sub-chronic As exposure exhibited similar cellular damage and shown to be phagocytosed by splenic macrophages, and these effects were mitigated by dietary Se supplementation. Furthermore, hydrogen peroxide treatment induced excessive phagocytosis of erythrocytes with As exposure by splenic macrophages, while co-treating erythrocytes with the reducing agent, N-Acetyl-l-cysteine, mitigated this excessive erythrophagocytosis. Hyperactivation of the NFκB pathway was also detected in splenic macrophages after excessive erythrophagocytosis. In conclusion, this study found that low Se status involving impaired redox homeostasis increased As retention in erythrocytes, which were subsequently phagocytosed by splenic macrophages and led to an increased inflammatory status of splenic macrophages. These findings provide insight into physiological features of arsenism related to Se status and redox homeostasis.
饮用水中砷（As）污染是一个全球性的公共健康问题。流行病学研究表明，硒（Se）缺乏与砷中毒风险增加有关。然而，Se 状态与红细胞中 As 保留之间的关系及其潜在机制尚未得到充分研究。在本研究中，共招募了 165 名合格受试者，发现 As 主要通过在红细胞中保留而在血液中积累。红细胞中 As 的保留与 Se 状态、与 Se 和 As 甲基化能力相关的抗氧化参数呈负相关，与 As 的蛋白结合能力呈正相关。此外，来自 Se 状态较低的受试者的红细胞表现出细胞损伤，同时 CD47 蛋白水平降低，而过氧化氢处理可加重这种损伤。与人体研究一致，亚慢性 As 暴露的小鼠红细胞表现出类似的细胞损伤，并被脾巨噬细胞吞噬，而膳食 Se 补充可减轻这些影响。此外，过氧化氢处理诱导脾巨噬细胞对暴露于 As 的红细胞进行过度吞噬，而用还原剂 N-乙酰-L-半胱氨酸共同处理红细胞可减轻这种过度的红细胞吞噬作用。在过度的红细胞吞噬作用后，还检测到脾巨噬细胞中 NFκB 通路的过度激活。总之，本研究发现，涉及氧化还原稳态受损的低 Se 状态增加了红细胞中 As 的保留，随后被脾巨噬细胞吞噬，并导致脾巨噬细胞的炎症状态增加。这些发现为与 Se 状态和氧化还原稳态相关的砷中毒的生理特征提供了深入了解。
