Tamoxifen-induced hepatotoxicity via lipid accumulation and inflammation in zebrafish. (January 2020)

• Record Type: Journal Article
• Authors: Yu, Qinwei; Huo, Jingting; Zhang, Yun; Liu, Kechun; Cai, Yu; Xiang, Ting; Jiang, Zhenzhou; Zhang, Luyong
• Is Part Of: Chemosphere. Volume 239(2020)
• Publication Date: 2020-01
• Subjects: Tamoxifen -- Zebrafish -- Aquatic ecotoxicity -- Liver injury -- Lipid accumulation; ER estrogen receptor -- NAFLD nonalcoholic fatty liver disease -- TC cholesterol -- TG triglyceride -- LDL low density lipoprotein -- ALT alanine aminotransferase -- hpf hours postfertilization -- hpe hours postexposure -- AST aminotransferase -- HE hematoxylin-eosin staining -- RT-PCR Real-Time polymerase chain reaction -- ISH In situ hybridization -- PPAR peroxisome proliferator-activated receptors -- Tnf α tumor necrosis factor α -- Il 1β interleukin 1β -- IL 6 interleukin 6 -- Srebf1/2 sterol regulatory element binding transcription factor 1/2 -- Fasn fatty acid synthase -- Acaca acetyl-coa carboxylase α -- Abca 1b ATP binding cassette subfamily a member 1b -- Lxr liver x receptor; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2019.124705
• Languages: English
• ISSNs: 0045-6535

Abstract

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. Graphical abstract: Image 1 Highlights: Residue of tamoxifen in sewage could cause aquatic ecotoxicity. Tamoxifen-induced toxicity in zebrafish mainly perform as hepatotoxicity. The mechanism of tamoxifen-induced aquatic liver injury is due to the increase of Srebf1, Srebf2 and Fasn gene.