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Environmentally relevant concentrations of tris (2-chloroethyl) phosphate (TCEP) induce hepatotoxicity in zebrafish (Danio rerio): a whole life-cycle assessment

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Abstract

Tris (2-chloroethyl) phosphate (TCEP), a typical organophosphate flame retardant, is of increasingly great concern considering their ubiquitous presence in aquatic environments and potential ecotoxicity. The present work was aimed to investigate the potential growth inhibition and hepatic stress induced by whole life-cycle exposure to TCEP (0.8, 4, 20 and 100 μg/L) in zebrafish. The results revealed that the body length, body mass and hepatic-somatic index (HSI) of zebrafish were significantly declined after exposure to TCEP for 120 days. GPx activity and GSH content were increased in the liver of zebrafish treated with low concentrations (0.8 and 4 μg/L) of TCEP, while exposure to high concentrations (20 and 100 μg/L) of TCEP reduced antioxidative capacity and elevated lipid peroxidation (LPO) levels. Gene transcription analysis demonstrated that the mRNA levels of nrf2 were altered in a similar manner to the transcription of the downstream genes nqo1 and hmox1, suggesting that Nrf2-Keap1 pathway mediated TCEP-induced oxidative stress in zebrafish liver. In addition, TCEP exposure might alleviate inflammatory response through down-regulating transcription of inflammatory cytokines (il-1β, il-6 and inos), and induce apoptosis via activating the p53-Bax pathway. Moreover, whole life-cycle exposure to TCEP caused a series of histopathological anomalies in zebrafish liver. Overall, our results revealed that lifetime exposure to environmentally relevant concentrations of TCEP could result in growth retardation and induce significant hepatotoxicity in zebrafish.

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Funding

This work was supported by National College Students Innovation and Entrepreneurship Training Program (China, 202310389025).

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Contributions

FH: Writing -Writing - Review & Editing, Investigation, Supervision, Project administration. WL: Conceptualization, Methodology, Validation, Investigation, Writing - original draft & Review, Funding acquisition. HW: Conceptualization, Methodology, Formal analysis, Investigation. HP: Validation, Visualization. JH: Investigation. JD: Validation. WZ: Validation. All the authors revised and approved the ms.

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Correspondence to Fengxiao Hu.

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The authors declare no competing interests.

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Our experimental protocols were approved by Laboratory Animals Ethics and Welfare Committee of College of Animal Science, Fujian Agriculture and Forestry University (PZCASFAFU22039).

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Highlights

Whole life-cycle exposure to environmental relevant concentrations of TCEP could inhibit the growth of zebrafish.

Exposure to TCEP induced oxidative stress and led to lipid peroxidation in zebrafish liver.

Inflammatory response might be alleviated through the down-regulation of inflammatory cytokines mRNA expression.

Whole life-cycle exposure to TCEP might induce apoptosis through the activation of p53-Bax pathway.

Whole life-cycle exposure to TCEP resulted in a series of histopathological anomalies in zebrafish liver.

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Hu, F., Li, W., Wang, H. et al. Environmentally relevant concentrations of tris (2-chloroethyl) phosphate (TCEP) induce hepatotoxicity in zebrafish (Danio rerio): a whole life-cycle assessment. Fish Physiol Biochem 49, 1421–1433 (2023). https://doi.org/10.1007/s10695-023-01265-7

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