期刊
JOURNAL OF HAZARDOUS MATERIALS
卷 283, 期 -, 页码 98-109出版社
ELSEVIER
DOI: 10.1016/j.jhazmat.2014.09.012
关键词
Polybrominated diphenyl ethers; Oxidative stress; NAD(+); Inflammation; Troxerutin
资金
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- National Natural Science Foundation of China [81171012]
- Natural Science Foundation of Jiangsu Province [BK20131127]
- Qinglan Project Scientific and Technological Innovation Team Training Program of Jiangsu College and University
- Major Fundamental Research Program of the Natural Science Foundation of the Jiangsu Higher Education Institutions of China [07KJA36029]
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-kappa B p65 and the acetylation of NF-kappa B 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. (C) 2014 Elsevier B.V. All rights reserved.
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