2. Academic Validation
  3. Tamoxifen-induced hepatotoxicity via lipid accumulation and inflammation in zebrafish

Tamoxifen-induced hepatotoxicity via lipid accumulation and inflammation in zebrafish

  • Chemosphere. 2020 Jan;239:124705. doi: 10.1016/j.chemosphere.2019.124705.
Qinwei Yu 1,  Jingting Huo 2,  Yun Zhang 3,  Kechun Liu 4,  Yu Cai 5,  Ting Xiang 6,  Zhenzhou Jiang 7,  Luyong Zhang 8
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China. Electronic address: yuqinwei7213@163.com.
  • 2 Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China. Electronic address: 1508668675@qq.com.
  • 3 Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China. Electronic address: xiaohan_0818@163.com.
  • 4 Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China. Electronic address: hliukch@sdas.org.
  • 5 Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China. Electronic address: 3184117168@qq.com.
  • 6 Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China. Electronic address: 15850659282@163.com.
  • 7 Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009, China. Electronic address: beaglejiang@cpu.edu.cn.
  • 8 Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China; Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: lyzhang@cpu.edu.cn.
PMID: 31479913 DOI: 10.1016/j.chemosphere.2019.124705
Abstract

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.

Keywords

Aquatic ecotoxicity; Lipid accumulation; Liver injury; Tamoxifen; Zebrafish.

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