Ye Liang, Hu Zhengping, Wang Hui, Zhu Haibo, Dong Zhaoju, Jiang Wanglin, Zhao Huijuan, Li Ning, Mi Wei, Wang Wenyan, Hu Xihou
School of Public Health and Management, Binzhou Medical University, Yantai, Shandong, PR China; Institute of Toxicology, Binzhou Medical University, Yantai, Shandong, PR China.
Medicine & Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, PR China.
PLoS One. 2015 Oct 12;10(10):e0140281. doi: 10.1371/journal.pone.0140281. eCollection 2015.
Tris-(2,3-dibromopropyl) isocyanurate (TDBP-TAZTO), an emerging brominated flame retardant, possesses the characteristics of candidate persistent organic pollutants and has displayed toxicity to fish and rodents. TDBP-TAZTO can pass through the blood brain barrier and accumulate in brain. However, the neurotoxicity of TDBP-TAZTO has not yet studied in rodents. We hypothesize that TDBP-TAZTO could induce the neurotoxicity in rat hippocampal neurons. The male adult rats were exposed to TDBP-TAZTO of 5 and 50 mg/kg by gavage, daily for 6 months. TDBP-TAZTO resulted in cognitive impairment and depression-like behaviors, which may be related with TDBP-TAZTO-induced hypothalamic-pituitary-adrenal axis hyperactivation, upregulation of inflammatory and oxidative stress markers, overexpression of pro-apoptotic proteins, downexpression of neurogenesis-related proteins in hippocampus, and hippocampal neurons damage in DG, CA1 and CA3 areas. Our findings suggested that TDBP-TAZTO induces significant hippocampal neurotoxicity, which provokes cognitive impairment and depression-like behaviors in adult rats. Therefore, this research will contribute to evaluate the neurotoxic effects of TDBP-TAZTO in human.
三(2,3 - 二溴丙基)异氰尿酸酯(TDBP - TAZTO)是一种新兴的溴化阻燃剂,具有持久性有机污染物候选物的特征,并且已对鱼类和啮齿动物表现出毒性。TDBP - TAZTO可穿过血脑屏障并在大脑中蓄积。然而,TDBP - TAZTO的神经毒性在啮齿动物中尚未得到研究。我们假设TDBP - TAZTO可诱导大鼠海马神经元的神经毒性。成年雄性大鼠每天经口灌胃给予5和50 mg/kg的TDBP - TAZTO,持续6个月。TDBP - TAZTO导致认知障碍和类似抑郁的行为,这可能与TDBP - TAZTO诱导的下丘脑 - 垂体 - 肾上腺轴过度激活、炎症和氧化应激标志物上调、促凋亡蛋白过表达、海马中神经发生相关蛋白的下调以及齿状回(DG)、CA1和CA3区的海马神经元损伤有关。我们的研究结果表明,TDBP - TAZTO可诱导显著的海马神经毒性,从而引发成年大鼠的认知障碍和类似抑郁的行为。因此,本研究将有助于评估TDBP - TAZTO对人类的神经毒性作用。