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

Area of Science:

• Environmental Toxicology
• Nephrology
• Pharmacology

Background:

• 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) is a flame retardant linked to kidney damage via oxidative stress.
• The precise mechanisms of BDE-47-induced nephrotoxicity are not fully elucidated.
• Troxerutin, a flavonoid, exhibits antioxidant and anti-inflammatory properties.

Purpose of the Study:

• To investigate the protective effects of troxerutin against BDE-47-induced kidney damage in mice.
• To elucidate the underlying molecular mechanisms, focusing on oxidative stress, inflammation, and specific signaling pathways.

Main Methods:

• Mice were treated with BDE-47 and subsequently with troxerutin.
• Assessed levels of reactive oxygen species (ROS), urine albumin-to-creatinine ratio (ACR), and inflammatory markers (COX-2, iNOS, NF-κB).
• Examined NLRP3 inflammasome components (NLRP3, ASC, caspase-1, IL-1β), SDF-1, CXCR4, and TXNIP expression; utilized immunoprecipitation and siRNA knockdown.

Main Results:

• Troxerutin significantly reduced ROS levels and ACR in BDE-47-treated mice.
• It decreased inflammatory markers (COX-2, iNOS, NF-κB) and NLRP3 inflammasome activation (NLRP3, ASC, caspase-1, IL-1β).
• Troxerutin inhibited BDE-47-induced increases in SDF-1, CXCR4, and TXNIP, with evidence of a direct CXCR4-TXNIP interaction.

Conclusions:

• Troxerutin ameliorates BDE-47-induced kidney injury by mitigating oxidative stress and inflammation.
• The protective effect involves the modulation of the CXCR4-TXNIP/NLRP3 inflammasome pathway.
• Troxerutin represents a potential therapeutic agent for managing kidney damage caused by environmental pollutants like BDE-47.