Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China.
Chemosphere. 2020 Jan;239:124705. doi: 10.1016/j.chemosphere.2019.124705. Epub 2019 Aug 29.
Tamoxifen is a clinical drug for estrogen receptor (ER)-positive breast cancer. Recently, it has been detected in aquatic environment. The residual drugs will produce certain biological activity and create a risk to aquatic organism when they enter the water environment. Therefore, it has great significance to study the ecotoxicity of tamoxifen. In the study, we used zebrafish as a model of aquatic to investigate the ecotoxic mechanism of tamoxifen to aquatic. We found that tamoxifen induced liver lipid accumulation in zebrafish, which showed a significant hepatotoxicity with smaller liver area and bigger yolk area. Though biochemical and pathologic measurement, tamoxifen treated group showed higher transaminase and lipid content. The elevated liver lipid synthesis might due to the increase of lipid metabolism related gene Srebf1, Srebf2 and Fasn. Moreover, inflammatory cytokine Tnf-α, Il-1β And Il-6 were increased. This result confirmed the toxicity of tamoxifen to aquatic, suggested liver injury was the main characteristic of its ecotoxicity. This study indicated it is important to avoid tamoxifen discharging into the aquatic ecology and provided a theoretical basis of prevention tamoxifen-induced ecotoxicity to aquatic.
他莫昔芬是一种用于治疗雌激素受体（ER）阳性乳腺癌的临床药物。最近，它已在水生环境中被检测到。残留药物进入水环境后，会产生一定的生物活性，对水生生物造成风险。因此，研究他莫昔芬的生态毒性具有重要意义。在这项研究中，我们使用斑马鱼作为水生模型，研究他莫昔芬对水生生物的生态毒性机制。我们发现他莫昔芬诱导了斑马鱼肝脏脂质积累，表现出明显的肝毒性，肝面积减小，卵黄面积增大。通过生化和病理测量，他莫昔芬处理组的转氨酶和脂质含量升高。肝脏脂质合成的增加可能是由于脂质代谢相关基因 Srebf1、Srebf2 和 Fasn 的增加。此外，炎症细胞因子 Tnf-α、Il-1β 和 Il-6 也增加了。这一结果证实了他莫昔芬对水生生物的毒性，表明肝损伤是其生态毒性的主要特征。本研究表明，避免他莫昔芬排放到水生生态系统中非常重要，并为预防他莫昔芬对水生生物的生态毒性提供了理论依据。
