Does hepatotoxicity interfere with endocrine activity in zebrafish (Danio rerio)?

Baumann, Lisa; Holbech, Henrik; Schmidt‐Posthaus, Heike; Moissl, Angela P.; Hennies, Mark; Tiedemann, Janina; Weltje, Lennart; Segner, Helmut; Braunbeck, Thomas

doi:10.1016/j.chemosphere.2019.124589

Cited by 20 publications

(11 citation statements)

References 42 publications

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“…However, without any direct measurement of gonadal aromatase expression and/or activity, such an inhibition of VTG might also reflect other endocrine mode of action such as androgenic or anti-estrogenic activity. Further, VTG inhibition as a consequence of liver toxicity has often been postulated but recent studies demonstrated that it is unlikely that hepatotoxic chemicals will interfere with the hepatic capacity for VTG synthesis (Ayobahan et al 2020, Baumann et al 2020. Consequently, developing models providing information on mechanisms of action of substances on gonadal aromatase appears relevant to refine the fish screening assay(s).…”

Section: Introductionmentioning

confidence: 99%

Refinement of an OECD test guideline for evaluating the effects of endocrine disrupting chemicals on aromatase gene expression and reproduction using novel transgenic cyp19a1a-eGFP zebrafish

et al. 2020

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Section: Introductionmentioning

confidence: 99%

Refinement of an OECD test guideline for evaluating the effects of endocrine disrupting chemicals on aromatase gene expression and reproduction using novel transgenic cyp19a1a-eGFP zebrafish

et al. 2020

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“…The liver tissue structure is changed after being damaged, usually resulting in hepatocyte enlargement, vacuolation, and necrosis [ 54 , 55 ]. Baumann et al (2020) observed that single cell necrosis of hepatocytes increased with exposure compound concentration in zebrafish [ 56 ]. And also, Gong et al (2020) observed the liver tissue of blunt snout bream from the hypoxia group presented the hepatocellular degenerations [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

The transcriptomic responses of blunt snout bream (Megalobrama amblycephala) to acute hypoxia stress alone, and in combination with bortezomib

Zhao

Pan

et al. 2022

BMC Genomics

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Background Blunt snout bream (Megalobrama amblycephala) is sensitive to hypoxia. A new blunt snout bream strain, “Pujiang No.2”, was developed to overcome this shortcoming. As a proteasome inhibitor, bortezomib (PS-341) has been shown to affect the adaptation of cells to a hypoxic environment. In the present study, bortezomib was used to explore the hypoxia adaptation mechanism of “Pujiang No.2”. We examined how acute hypoxia alone (hypoxia-treated, HN: 1.0 mg·L− 1), and in combination with bortezomib (hypoxia-bortezomib-treated, HB: Use 1 mg bortezomib for 1 kg fish), impacted the hepatic ultrastructure and transcriptome expression compared to control fish (normoxia-treated, NN). Results Hypoxia tolerance was significantly decreased in the bortezomib-treated group (LOEcrit, loss of equilibrium, 1.11 mg·L− 1 and 1.32 mg·L− 1) compared to the control group (LOEcrit, 0.73 mg·L− 1 and 0.85 mg·L− 1). The HB group had more severe liver injury than the HN group. Specifically, the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the HB group (52.16 U/gprot, 32 U/gprot) were significantly (p < 0.01) higher than those in the HN group (32.85 U/gprot, 21. 68 U/gprot). In addition, more severe liver damage such as vacuoles, nuclear atrophy, and nuclear lysis were observed in the HB group. RNA-seq was performed on livers from the HN, HB and NN groups. KEGG pathway analysis disclosed that many DEGs (differently expressed genes) were enriched in the HIF-1, FOXO, MAPK, PI3K-Akt and AMPK signaling pathway and their downstream. Conclusion We explored the adaptation mechanism of “Pujiang No.2” to hypoxia stress by using bortezomib, and combined with transcriptome analysis, accurately captured the genes related to hypoxia tolerance advantage.

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“…Also here, nonstandard studies are ongoing to address the problem, e.g. screening for potential endocrine biomarkers through analysis of gene expression profiles [10,74]. Another role of non-standardised research is to identify new or additional types of hazards, i.e.…”

Section: Non-standard Studies Contribute To the Risk Management Under...mentioning

confidence: 99%

Characterisation and analysis of key studies used to restrict substances under REACH

2022

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Background Understanding how scientific studies are used in regulatory risk assessments is important since it influences the outcome of an assessment, and thus the level of protection of human health and the environment. Within the REACH legislation (Registration, Evaluation, Authorisation and Restriction of Chemicals, EC Nr. 1907/2006) hazard information on clearly defined (eco-)toxicological endpoints are submitted for the registration of substances, and this information is intended for concluding on potential hazards and risk as well as subsequent risk management measures such as restrictions. The present study aimed to (1) characterise key studies used by the European Chemicals Agency’s Committee for Risk Assessment to restrict hazardous substances; (2) analyse if the REACH registration database provided the key studies used in these restrictions, and (3) investigate potential expert disagreements related to the use of non-standard studies in the restrictions. Results Our analysis showed that 58% of the 53 scrutinised key studies were non-standard studies, all available by paying a fee or through open access. Sixteen (30%) of the key studies were consulted from external sources outside the REACH registration database by the Committee for Risk Assessment. Only one study of the 16 external key studies was a standard study. Further, 9% (5/53) of the key studies used by the Committee for Risk Assessment were inaccessible to third parties, all were standard studies. The uses of non-standard studies were (unsuccessfully) challenged for five substances during the public consultation. Conclusions These results suggest that non-standard studies contributed to the identification and management of substances of concern, that the REACH registration database may not be sufficient for the identification and management of uncontrolled hazards and risks, and that the transparency of the decisions made by the Committee for Risk Assessment was partially hampered due to the use of standard studies inaccessible to third parties.

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Does hepatotoxicity interfere with endocrine activity in zebrafish (Danio rerio)?

Cited by 20 publications

References 42 publications

Refinement of an OECD test guideline for evaluating the effects of endocrine disrupting chemicals on aromatase gene expression and reproduction using novel transgenic cyp19a1a-eGFP zebrafish

Refinement of an OECD test guideline for evaluating the effects of endocrine disrupting chemicals on aromatase gene expression and reproduction using novel transgenic cyp19a1a-eGFP zebrafish

The transcriptomic responses of blunt snout bream (Megalobrama amblycephala) to acute hypoxia stress alone, and in combination with bortezomib

Characterisation and analysis of key studies used to restrict substances under REACH

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