The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang 550025, China.
Oxid Med Cell Longev. 2022 Apr 25;2022:9865606. doi: 10.1155/2022/9865606. eCollection 2022.
Arsenic poisoning is a geochemical disease that seriously endangers human health. The liver is one of the important target organs for arsenic poisoning, several studies have shown that oxidative stress plays an important role in arsenic-induced liver damage. However, the specific mechanism of arsenic-induced oxidative stress has not yet been fully elucidated, and currently, there are no effective intervention measures for the prevention and treatment of arsenic-induced liver damage. In this study, the effect of the Nrf2/GPX4 signaling pathway and oxidative stress in the arsenic-induced liver damage was first evaluated. The results show that arsenic can activate the Nrf2/GPX4 signaling pathway and increase the oxidative stress, which in turn promotes arsenic-induced liver damage in MIHA cells. Moreover, when we applied the Nrf2 inhibitor, the promoting effect of arsenic on liver damage was alleviated by inhibiting the activation of the Nrf2/GPX4 signaling pathway. Subsequently, the Rosa roxburghii Tratt [Rosaceae] (RRT) intervention experiments in cells and arsenic poisoning population were designed. The results revealed that RRT can inhibit Nrf2/GPX4 signaling pathway to reduce oxidative stress, thereby alleviates arsenic-induced liver damage. This study provides some limited evidence that arsenite can activate Nrf2/GPX4 signaling pathway to induce oxidative stress, which in turn promotes arsenic-induced liver damage in MIHA cells. The second major finding was that Kaji-ichigoside F1 may be a potential bioactive compound of RRT, which can inhibit Nrf2/GPX4 signaling pathway to reduce oxidative stress, thereby alleviates arsenic-induced liver damage. Our study will contribute to a deeper understanding of the mechanisms in arsenic-induced liver damage, these findings will identify a possible natural medicinal food dual-purpose fruit, RRT, as a more effective prevention and control strategies for arsenic poisoning.
砷中毒是一种严重危害人类健康的地球化学疾病。肝脏是砷中毒的重要靶器官之一，已有多项研究表明，氧化应激在砷诱导的肝损伤中起重要作用。然而，砷诱导的氧化应激的具体机制尚未完全阐明，目前尚无有效的干预措施来预防和治疗砷诱导的肝损伤。本研究首先评估了 Nrf2/GPX4 信号通路和氧化应激在砷诱导肝损伤中的作用。结果表明，砷可以激活 Nrf2/GPX4 信号通路，增加氧化应激，进而促进 MIHA 细胞中的砷诱导肝损伤。此外，当我们应用 Nrf2 抑制剂时，通过抑制 Nrf2/GPX4 信号通路的激活，减轻了砷对肝损伤的促进作用。随后，在细胞和砷中毒人群中设计了罗梭桃 [蔷薇科]（RRT）干预实验。结果表明，RRT 可以抑制 Nrf2/GPX4 信号通路，减少氧化应激，从而减轻砷诱导的肝损伤。本研究提供了一些有限的证据表明，亚砷酸盐可以激活 Nrf2/GPX4 信号通路诱导氧化应激，进而促进 MIHA 细胞中的砷诱导肝损伤。第二个主要发现是，奇果素 F1 可能是 RRT 的一种潜在生物活性化合物，它可以抑制 Nrf2/GPX4 信号通路，减少氧化应激，从而减轻砷诱导的肝损伤。我们的研究将有助于更深入地了解砷诱导肝损伤的机制，这些发现将确定罗梭桃作为一种更有效的砷中毒预防和控制策略的可能天然药食两用水果。
