School of Environment Science and Spatial Informatics, China University of Mining and Technology, Xuzhou, 221008 Jiangsu, China.
Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, 101 Shanghai Road, Xuzhou, 221116 Jiangsu, China.
Oxid Med Cell Longev. 2018 Apr 19;2018:9865495. doi: 10.1155/2018/9865495. eCollection 2018.
2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) induces oxidative stress in kidney cells, but the underlying mechanism remains poorly understood. Troxerutin, a natural flavonoid, has potential antioxidant and anti-inflammatory efficacy. In this study, we assessed the effect of troxerutin on kidney damage caused by BDE-47 and investigated the underlying mechanism. The results showed troxerutin reduced reactive oxygen species (ROS) level and urine albumin-to-creatinine ratio (ACR), decreased the activities of inflammatory factors including cyclooxygenase-2 (COX-2), induced nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-B) in the kidney tissues of BDE-47-treated mice. Furthermore, troxerutin significantly weakened the expression of kidney NLRP3 inflammasome containing NLRP3, ASC, and caspase-1, contributing to the decline of IL-1. Additionally, troxerutin inhibited the increased protein level of stromal-derived factor-1(SDF-1), C-X-C chemokine ligand 12 receptor 4 (CXCR4), and thioredoxin interaction protein (TXNIP) caused by BDE-47. Specifically, the immunoprecipitation assay indicated that there was a direct interaction between CXCR4 and TXNIP. CXCR4 siRNA and TXNIP siRNA also decreased the inflammatory damage, which was similar to the action of troxerutin. Our data demonstrated that troxerutin regulated the inflammatory lesions via CXCR4-TXNIP/NLRP3 inflammasome in the kidney of mice induced by BDE-47.
2,2',4,4'-四溴二苯醚（BDE-47）可诱导肾细胞氧化应激，但其中的作用机制尚不清楚。曲克芦丁是一种天然黄酮类化合物，具有潜在的抗氧化和抗炎作用。在本研究中，我们评估了曲克芦丁对 BDE-47 引起的肾损伤的作用，并探讨了其作用机制。结果表明，曲克芦丁可降低活性氧（ROS）水平和尿白蛋白/肌酐比（ACR），降低 BDE-47 处理小鼠肾组织中环氧化酶-2（COX-2）、诱导型一氧化氮合酶（iNOS）和核因子 kappa B（NF-B）等炎症因子的活性。此外，曲克芦丁可显著减弱 NLRP3 炎性小体中包含的 NLRP3、ASC 和半胱氨酸天冬氨酸蛋白酶-1（caspase-1）的表达，从而导致白细胞介素-1（IL-1）水平下降。此外，曲克芦丁抑制了 BDE-47 引起的基质衍生因子-1（SDF-1）、C-X-C 趋化因子配体 12 受体 4（CXCR4）和硫氧还蛋白相互作用蛋白（TXNIP）蛋白水平的增加。具体来说，免疫沉淀实验表明，CXCR4 和 TXNIP 之间存在直接相互作用。CXCR4 siRNA 和 TXNIP siRNA 也可减轻炎症损伤，作用与曲克芦丁相似。我们的数据表明，曲克芦丁通过 BDE-47 诱导的小鼠肾中 CXCR4-TXNIP/NLRP3 炎性小体调节炎症病变。
