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

Abstract

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.

Troxerutin Prevents 5-Fluorouracil Induced Morphological Changes in the Intestinal Mucosa: Role of Cyclooxygenase-2 Pathway

“…The body weight of mice was assessed daily prior to administration of the administered treatment to confirm the experimental model of 5-FU induced intestinal mucositis. The TRX doses considered in the current study are in accordance with those in previous published studies [19][20][21][22]61]. daily prior to administration of the administered treatment to confirm the experimental model of 5-FU induced intestinal mucositis.…”

“…daily prior to administration of the administered treatment to confirm the experimental model of 5-FU induced intestinal mucositis. The TRX doses considered in the current study are in accordance with those in previous published studies [19][20][21][22]61]. To investigate the role of cyclooxygenase 2 (COX-2) enzyme during TRX treatment of 5-FUinduced intestinal mucositis, COX-2 was blocked by an intraperitoneal (i.p) injection of 7.5 mg/kg of CLX.…”

“…Troxerutin (TRX) is a semi-synthetic flavonoid, derived from rutin, which is extracted from Dimorphandra gardneriana. This compound has various pharmacological activities, including antioxidant [17][18][19], anti-inflammatory [20], anti-apoptotic [21,22], and antiedematogenic [23,24]. Further, it is a potent therapeutic agent for neuropathic pain [25].…”

Troxerutin acts on complement mediated inflammation to ameliorate arthritic symptoms in rats

“…It is widely reported that TXR is a phytochemical with proven health benefits. It also has a very low toxicity (LD 50 of 27160 mg/kg body weight in rat) and safe for human use [38][39][40][41] .…”

Identification of robust genetic signatures associated with lipopolysaccharide-induced acute lung injury onset and astaxanthin therapeutic effects by integrative analysis of RNA sequencing data and GEO datasets

“…In response to the increased formation of reactive oxygen species (ROS), thioredoxin interacting protein (TXNIP) detaches from thioredoxin (Trx), binds to the nucleotide-binding domain-like receptor protein 3 (NLRP3), and then activates NLRP3 inflammasome [ 8 ]. The activation of the NLRP3 inflammasome results in the maturation and release of pro-inflammatory cytokines, such as interleukin-1β (IL-1β), which further aggravates the production of inflammatory cytokines (tumor necrosis factor-α (TNF-α), IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX2)) and induces oxidative stress [ 9 – 11 ].…”