CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan , Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences (CAS), Wuhan National Research Center for Optoelectronics , Wuhan 430071 , P. R. China.
University of Chinese Academy of Sciences , Beijing 100049 , P. R. China.
Chem Res Toxicol. 2019 Nov 18;32(11):2320-2328. doi: 10.1021/acs.chemrestox.9b00316. Epub 2019 Oct 14.
Environmental exposure to triclocarban (TCC), a common antibacterial agent widely used in thousands of personal care products, poses a potential risk for human health. Previous in vitro studies about biological effects of TCC have yielded a variety of inconsistent results and apparently not been verified in vivo. In the current study, dose-dependent effects of TCC exposure on lipid homeostasis in rats were investigated using a combination of untargeted H NMR metabolomics, targeted metabolite profiling (LC/GC-MS), histopathological assessments, and biological assays. Our results revealed that TCC dose-dependently activated aryl hydrocarbon receptor (AHR) and its transcriptional targets such as and in the liver of rats, suggesting that TCC may be a potent AHR agonist. Although TCC exhibited dose-dependent toxicity, oral exposure with relatively low dose TCC caused more significant hepatic lipogenesis of rats than relatively high and moderate doses of TCC. It was mainly manifested by histopathological observations and promotion of de novo fatty acid, phospholipid, and ceramide biosynthesis and gut microbiota fermentation. Our findings provide new insights into health effects of TCC exposure with different dosages in vivo, especially on the induction and progression of nonalcoholic fatty liver disease, and further our understanding in the pathogenesis of metabolic diseases induced by environmental pollutants.
环境暴露于三氯生（TCC），一种广泛用于数千种个人护理产品的常见抗菌剂，对人类健康构成潜在风险。先前关于 TCC 生物效应的体外研究产生了各种不一致的结果，显然尚未在体内得到验证。在当前的研究中，使用非靶向性 1 H NMR 代谢组学、靶向代谢物分析（LC/GC-MS）、组织病理学评估和生物测定相结合的方法，研究了 TCC 暴露对大鼠脂质稳态的剂量依赖性影响。我们的结果表明，TCC 剂量依赖性地激活了大鼠肝脏中的芳香烃受体（AHR）及其转录靶标，如 和 ，这表明 TCC 可能是一种有效的 AHR 激动剂。尽管 TCC 表现出剂量依赖性毒性，但口服相对低剂量 TCC 暴露比相对高剂量和中等剂量 TCC 更显著地促进了大鼠的肝内脂肪生成。这主要表现为组织病理学观察以及促进从头脂肪酸、磷脂和神经酰胺生物合成和肠道微生物群发酵。我们的研究结果为体内不同剂量 TCC 暴露的健康影响提供了新的见解，特别是对非酒精性脂肪性肝病的诱导和进展的影响，并进一步加深了我们对环境污染物引起的代谢性疾病发病机制的理解。
