Troxerutin Protects Kidney Tissue against BDE-47-Induced Inflammatory Damage through CXCR4-TXNIP/NLRP3 Signaling

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-κB) 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-1β. 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.