State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, 163 Xianlin Avenue, Nanjing, Jiangsu 210023, People's Republic of China.
Key Laboratory of Pathogen Biology of Jiangsu Province, Department of Pathogen Biology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu 211166, People's Republic of China.
Environ Sci Technol. 2020 Aug 18;54(16):10149-10158. doi: 10.1021/acs.est.0c01543. Epub 2020 Jul 29.
1,4-Dioxane is a widely used industrial solvent that has been frequently detected in aquatic environments. However, the hepatotoxicity of long-term dioxane exposure at environmentally relevant concentrations and underlying mechanisms of liver damage remain unclear. In this study, male mice were exposed to dioxane at concentrations of 0.5, 5, 50, and 500 ppm for 12 weeks, followed by histopathological examination of liver sections and multiomics investigation of the hepatic transcriptome, serum metabolome, and gut microbiome. Results showed that dioxane exposure at environmentally relevant concentrations induced hepatic inflammation and caused changes in the hepatic transcriptome and serum metabolic profiles. However, no inflammatory response was observed after exposure to all concentrations of dioxane and its metabolites. The gut microbiome was considered to be contributing to this apparently contradictory response. Increased levels of lipopolysaccharide (LPS) may be produced by some gut microbiota, such as Porphyromonadaceae and Helicobacteraceae, after 500 ppm of dioxane exposure. LPS may enter the blood circulation through an impaired intestinal wall and aggravate hepatic inflammation in mice. This study provides novel insight into the underlying mechanisms of hepatic inflammation induced by dioxane and highlights the need for concerns about environmentally relevant concentrations of dioxane exposure.
1,4-二恶烷是一种广泛使用的工业溶剂，经常在水生环境中检测到。然而，长期暴露于环境相关浓度的二恶烷的肝毒性及其潜在的肝损伤机制尚不清楚。在这项研究中，雄性小鼠暴露于浓度为 0.5、5、50 和 500ppm 的二恶烷中 12 周，然后对肝组织切片进行组织病理学检查，并对肝转录组、血清代谢组和肠道微生物组进行多组学研究。结果表明，环境相关浓度的二恶烷暴露可诱导肝炎症，并导致肝转录组和血清代谢谱发生变化。然而，在暴露于所有浓度的二恶烷及其代谢物后，均未观察到炎症反应。肠道微生物组被认为是导致这种明显矛盾反应的原因之一。在暴露于 500ppm 的二恶烷后，某些肠道微生物（如卟啉单胞菌科和螺旋杆菌科）可能会产生更多的脂多糖（LPS）。LPS 可能通过受损的肠壁进入血液，并加重小鼠的肝炎症。本研究为二恶烷诱导肝炎症的潜在机制提供了新的见解，并强调了对环境相关浓度的二恶烷暴露的关注的必要性。
