Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Department of Land, Air and Water Resources, University of California, Davis, CA, 95616, USA.
Environ Pollut. 2020 Oct;265(Pt A):114995. doi: 10.1016/j.envpol.2020.114995. Epub 2020 Jun 10.
Triclosan (TCS) and its two derivatives (2,4-dichlorophenol and 2,4,6-trichlorophenol) are priority pollutants that coexist in aquatic environments. Joint exposure of TCS, 2,4-dichlorophenol and 2,4,6-trichlorophenol, hereafter referred to as TCS-DT, contributes severe toxicity to aquatic organisms. There is currently a paucity of data regarding TCS-DT molecular toxicity, especially on cardiac diseases. We used zebrafish (Danio rerio) as a model organism, and evaluated the molecular-level cardiotoxicity induced by TCS-DT from embryonic to adult stages. TCS-DT exposure prominently led to phenotypic malformations, such as pericardial cysts, cardiac bleeding, increased SV-BA distance, decreased heart rate and reduced ejection fraction, as well as abnormal swimming behavior. Analyses of the GO and KEGG pathways revealed enrichment pathways related to cardiac development and screened for significantly down-regulated adrenaline signaling in cardiomyocytes. The cardiac marker genes (amhc, cmlc2, vmhc, and nkx2.5) were obtained through protein-protein interaction (PPI) networks, and expressed as down-regulation by WISH. After chronic exposure to TCS-DT from 30 to 90-dpf, both body mass and heart indexes prominently increased, showing myocardial hypertrophy, abnormal heart rate and histopathological injury. Heart tissue damage included disordered and ruptured myocardial fibers, broken and dissolved myofilaments, nuclear pyknosis, mitochondrial injury and inflammatory cell infiltration. Further, abnormal changes in a series of cardiac functions-related biomarkers, including superoxide dismutase, triglyceride, lactate dehydrogenase and creatinine kinase MB, provided evidence for cardiac pathological responses. These results highlight the molecular mechanisms involving TCS-DT induced cardiac toxicity, and provide theoretical data to guide prevention and treatment of pollutant-induced cardiac diseases.
三氯生（TCS）及其两种衍生物（2,4-二氯苯酚和 2,4,6-三氯苯酚）是共存于水环境中的优先污染物。TCS、2,4-二氯苯酚和 2,4,6-三氯苯酚的联合暴露（简称 TCS-DT）对水生生物具有严重毒性。目前关于 TCS-DT 分子毒性的数据很少，特别是关于心脏病的。我们使用斑马鱼（Danio rerio）作为模型生物，从胚胎到成年阶段评估 TCS-DT 引起的分子水平心脏毒性。TCS-DT 暴露显著导致表型畸形，如心包囊肿、心脏出血、SV-BA 距离增加、心率降低和射血分数降低，以及异常游泳行为。GO 和 KEGG 通路分析揭示了与心脏发育相关的富集通路，并筛选出心肌细胞中肾上腺素信号显著下调。通过蛋白质-蛋白质相互作用（PPI）网络获得心脏标志物基因（amhc、cmlc2、vmhc 和 nkx2.5），并通过 WISH 显示为下调。在 30 至 90-dpf 期间慢性暴露于 TCS-DT 后，体重和心脏指数均显著增加，表现为心肌肥厚、心率异常和组织病理学损伤。心脏组织损伤包括心肌纤维排列紊乱和破裂、肌丝断裂和溶解、核固缩、线粒体损伤和炎性细胞浸润。此外，一系列与心脏功能相关的生物标志物的异常变化，包括超氧化物歧化酶、甘油三酯、乳酸脱氢酶和肌酸激酶 MB，为心脏病理反应提供了证据。这些结果强调了 TCS-DT 诱导心脏毒性的分子机制，并为指导预防和治疗污染物诱导的心脏病提供了理论数据。
