Abstract：
The ubiquitous environmental presence of tris(2-chloroethyl) phosphate (TCEP) poses a potential threat to animals; however, little is known about its hepatotoxicity. In this study, the effects of TCEP exposure (0.5 and 5.0 μg/L for 28 days) on liver health and the potential underlying toxification mechanisms were investigated in zebrafish. Our results demonstrated that TCEP exposure led to hepatic tissue lesions and resulted in significant alterations in liver-injury-specific markers. Moreover, TCEP-exposed fish had significantly lower levels of thyrotropin-releasing hormone and thyroid-stimulating hormone in the brain, evidently less triiodothyronine whereas more thyroxine in plasma, and markedly altered expressions of genes from the hypothalamic-pituitary-thyroid (HPT) axis in the brain or liver. In addition, a significantly higher proportion of Bacteroidetes in the gut microbiota, an elevated bacterial source endotoxin lipopolysaccharide (LPS) in the plasma, upregulated expression of LPS-binding protein and Toll-like receptor 4 in the liver, and higher levels of proinflammatory cytokines in the liver were detected in TCEP-exposed zebrafish. Furthermore, TCEP-exposed fish also suffered severe oxidative damage, possibly due to disruption of the antioxidant system. These findings suggest that TCEP may exert hepatotoxic effects on zebrafish by disrupting the HPT and gut-liver axes and thereafter inducing hepatic inflammation and oxidative stress.
摘要：
环境中普遍存在的磷酸三(2-氯乙基)酯(TCEP)对动物构成潜在威胁;然而,对它的肝毒性知之甚少。在这项研究中,在斑马鱼中研究了TCEP暴露（0.5和5.0μg/L，持续28天）对肝脏健康的影响以及潜在的潜在潜在的潜在毒性机制。我们的结果表明，TCEP暴露导致肝组织病变，并导致肝损伤特异性标志物的显着改变。此外，TCEP暴露的鱼类大脑中的促甲状腺激素释放激素和促甲状腺激素的水平显着降低，血浆中的三碘甲状腺原氨酸明显较少，而甲状腺素较多，并显着改变了大脑或肝脏中下丘脑-垂体-甲状腺（HPT）轴的基因表达。此外,肠道微生物群中的拟杆菌比例明显更高，血浆中细菌来源内毒素脂多糖（LPS）升高，LPS结合蛋白和Toll样受体4在肝脏中的表达上调,在TCEP暴露斑马鱼中检测到肝脏中更高水平的促炎细胞因子。此外，TCEP暴露的鱼类也遭受了严重的氧化损伤，可能是由于抗氧化系统的破坏。这些发现表明，TCEP可能通过破坏HPT和肠-肝轴并随后诱导肝脏炎症和氧化应激对斑马鱼产生肝毒性作用。
