Department of Health Laboratory Technology, School of Public Health, China Medical University, Shenyang, 110122, PR China.
Department of Health Laboratory Technology, School of Public Health, China Medical University, Shenyang, 110122, PR China; Key Laboratory of Arsenic-related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang, 110122, PR China.
J Ethnopharmacol. 2021 Dec 5;281:114584. doi: 10.1016/j.jep.2021.114584. Epub 2021 Aug 29.
Realgar is a traditional Chinese medicine used in China for a long history. Long-time or excessive use of realgar causes liver injury. However, its underlying mechanism is not fully clarified.
In this study, we investigated the toxic effect of sub-chronic exposure to realgar on mice liver, and further revealed its underlying mechanism focused on the TXNIP/NLRP3 pathway and bile acid homeostasis.
Mice were divided into control and different doses of sub-chronic realgar exposed groups. Total arsenic levels in the blood and liver were determined by atomic fluorescence spectrometry. The effect of realgar on liver function was evaluated by biochemical analysis and histopathological examination. Assay kits were applied for the measurement of oxidative stress indexes, MPO and plasma inflammatory cytokines. The mRNA and proteins involved in the TXNIP/NLRP3 and NF-κB pathways were determined by RT-qPCR, western blot, Immunofluorescence and Immunohistochemistry. UHPLC/MS/MS was used for the quantitative analysis of bile acids (BAs) in mice plasma, liver and urine. The genes related to BAs metabolism were measured by RT-qPCR.
Sub-chronic exposure to realgar led to arsenic accumulation and caused oxidative damage and inflammatory infiltration in mouse liver, finally resulting in liver injury. Realgar treatment activated the NF-κB pathway and significantly upregulated the TXNIP/NLRP3 pathway in mouse liver. Realgar altered the metabolic balance of BAs, which is related to the abnormal expression of BAs transporters and enzymes.
Sub-chronic exposure to realgar caused liver injury in mouse, and the mechanism may involve the upregulation of the TXNIP/NLRP3 pathway and disordered BAs homeostasis.
雄黄是一种在中国长期使用的传统中药。长期或过量使用雄黄会导致肝损伤。然而，其潜在机制尚未完全阐明。
本研究旨在探讨雄黄亚慢性暴露对小鼠肝脏的毒性作用，并进一步揭示其潜在机制，重点关注 TXNIP/NLRP3 途径和胆汁酸稳态。
将小鼠分为对照组和不同剂量的雄黄亚慢性暴露组。采用原子荧光光谱法测定血液和肝脏中的总砷含量。通过生化分析和组织病理学检查评价雄黄对肝功能的影响。试剂盒用于测定氧化应激指标、MPO 和血浆炎症细胞因子。采用 RT-qPCR、western blot、免疫荧光和免疫组织化学测定参与 TXNIP/NLRP3 和 NF-κB 途径的 mRNA 和蛋白。采用 UHPLC/MS/MS 定量分析小鼠血浆、肝脏和尿液中的胆汁酸（BAs）。采用 RT-qPCR 测定与 BAs 代谢相关的基因。
雄黄亚慢性暴露导致砷蓄积，引起小鼠肝脏氧化损伤和炎症浸润，最终导致肝损伤。雄黄处理激活了 NF-κB 途径，并显著上调了小鼠肝脏中的 TXNIP/NLRP3 途径。雄黄改变了 BAs 的代谢平衡，这与 BAs 转运体和酶的异常表达有关。
雄黄亚慢性暴露导致小鼠肝脏损伤，其机制可能涉及 TXNIP/NLRP3 途径的上调和 BAs 稳态的紊乱。
