Troxerutin protects against 2,2',4,4'-tetrabromodiphenyl ether (BDE-47)-induced liver inflammation by attenuating oxidative stress-mediated NAD⁺-depletion.

Abstract

Emerging evidence indicates that 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) induces liver injury through enhanced ROS production and lymphocytic infiltration, which may promote a liver inflammatory response. Antioxidants have been reported to attenuate the cellular toxicity associated with polybrominated diphenyl ethers (PBDEs). In this study, we investigated the effect of troxerutin, a trihydroxyethylated derivative of the natural bioflavonoid rutin, on BDE-47-induced liver inflammation and explored the potential mechanisms underlying this effect. Our results showed that NAD(+)-depletion was involved in the oxidative stress-mediated liver injury in a BDE-47 treated mouse model, which was confirmed by Vitamin E treatment. Furthermore, our data revealed that troxerutin effectively alleviated liver inflammation by mitigating oxidative stress-mediated NAD(+)-depletion in BDE-47 treated mice. Consequently, troxerutin remarkably restored SirT1 protein expression and activity in the livers of BDE-47-treated mice. Mechanistically, troxerutin dramatically repressed the nuclear translocation of NF-κB p65 and the acetylation of NF-κB p65 (Lys 310) and Histone H3 (Lys9) to abate the transcription of inflammatory genes in BDE-47-treated mouse livers. These inhibitory effects of troxerutin were markedly blunted by EX527 (SirT1 inhibitor) treatment. This study provides novel mechanistic insights into the toxicity of BDE-47 and indicates that troxerutin might be used in the prevention and therapy of BDE-47-induced hepatotoxicity.

• Authors: Zi-Feng Zhang, Yan-Qiu Zhang, Shao-Hua Fan, Juan Zhuang, Yuan-Lin Zheng, Jun Lu, Dong-Mei Wu, Qun Shan, Bin Hu
• Journal: Journal of hazardous materials (J Hazard Mater) Vol. 283 Pg. 98-109 ( 2015) ISSN: 1873-3336 [Electronic] Netherlands
• PMID: 25262482 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Antioxidants
• Halogenated Diphenyl Ethers
• Hazardous Substances
• Hydroxyethylrutoside
• NF-kappa B
• 2,2',4,4'-tetrabromodiphenyl ether
• troxerutin

Topics

• Animals
• Antioxidants (pharmacology)
• Halogenated Diphenyl Ethers (toxicity)
• Hazardous Substances (toxicity)
• Hydroxyethylrutoside (analogs & derivatives, pharmacology)
• Liver (metabolism)
• Mice
• NF-kappa B (metabolism)
• Oxidative Stress (drug effects)