A high-throughput screening assay for identification of chemicals with liver tumor promoting potential using a transgenic zebrafish line

Chen, Sheng; Wu, Jian; Li, Meng; Sun, Qian; Gong, Zhiyuan; Letcher, Robert J.; Liu, Chunsheng

doi:10.1016/j.chemosphere.2022.134169

Cited by 3 publications

(1 citation statement)

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“…The hepatotoxicity of TCEP in zebrafish was evaluated by histopathological observation according to standard laboratory procedures (a detailed experimental protocol is given in the SI). 56 To further confirm the hepatotoxicity of TCEP, liver-injuryspecific biomarkers including AST, ALT, and ALP were determined following the reported methods (detailed experimental protocols are explained in the SI) using the corresponding commercial kits (BC1560, BC1550, and BC2140, respectively; Solarbio, Beijing, China). 57−59 2.4.…”

Section: Assessment Of Hepatotoxicity Of Tcep To Zebrafishmentioning

confidence: 99%

Tris(2-chloroethyl) Phosphate Exerts Hepatotoxic Impacts on Zebrafish by Disrupting Hypothalamic–Pituitary–Thyroid and Gut–Liver Axes

Tian

et al. 2023

Environ. Sci. Technol.

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The ubiquitous environmental presence of tris(2chloroethyl) phosphate (TCEP) poses a potential threat to animals; however, little is known about its hepatotoxicity. In this study, the effects of TCEP exposure (0.5 and 5.0 μg/L for 28 days) on liver health and the potential underlying toxification mechanisms were investigated in zebrafish. Our results demonstrated that TCEP exposure led to hepatic tissue lesions and resulted in significant alterations in liver-injury-specific markers. Moreover, TCEP-exposed fish had significantly lower levels of thyrotropin-releasing hormone and thyroid-stimulating hormone in the brain, evidently less triiodothyronine whereas more thyroxine in plasma, and markedly altered expressions of genes from the hypothalamic−pituitary−thyroid (HPT) axis in the brain or liver. In addition, a significantly higher proportion of Bacteroidetes in the gut microbiota, an elevated bacterial source endotoxin lipopolysaccharide (LPS) in the plasma, upregulated expression of LPSbinding protein and Toll-like receptor 4 in the liver, and higher levels of proinflammatory cytokines in the liver were detected in TCEP-exposed zebrafish. Furthermore, TCEP-exposed fish also suffered severe oxidative damage, possibly due to disruption of the antioxidant system. These findings suggest that TCEP may exert hepatotoxic effects on zebrafish by disrupting the HPT and gut− liver axes and thereafter inducing hepatic inflammation and oxidative stress.

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Section: Assessment Of Hepatotoxicity Of Tcep To Zebrafishmentioning

confidence: 99%