scholarly journals Lethal and Sub-Lethal Effects and Modulation of Gene Expression Induced by T Kinase Inhibitors in Zebrafish (Danio Rerio) Embryos

Toxics ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 4
Author(s):  
Tina Elersek ◽  
Matjaž Novak ◽  
Mateja Mlinar ◽  
Igor Virant ◽  
Nika Bahor ◽  
...  

Tyrosine kinase inhibitors (TKIs) are designed for targeted cancer therapy. The consumption of these drugs during the last 20 years has been constantly rising. In the zebrafish (Danio rerio) embryo toxicity test, we assessed the toxicity of six TKIs: imatinib mesylate, erlotinib, nilotinib, dasatinib, sorafenib and regorafenib. Imatinib mesylate and dasatinib induced lethal effects, while regorafenib, sorfenib and dasatinib caused a significant increase of sub-lethal effects, predominantly oedema, no blood circulation and formation of blood aggregates. The analyses of the changes in the expression of selected genes associated with the hormone system after the exposure to imatinib mesylate, dasatinib and regorafenib demonstrated that all three tested TKIs deregulated the expression of oestrogen receptor esr1, cytochrome P450 aromatase (cypa19b) and hydroxysteroid-dehydrogenase (hsd3b), regorafenib, and also thyroglobulin (tg). The expression of genes involved in the DNA damage response (gadd45 and mcm6) and apoptosis (bcl2) was deregulated only by exposure to regorafenib. The data indicate that common mechanisms, namely antiangiogenic activity and interference with steroidogenesis are involved in the TKI induced sub-lethal effects and potential hormone disrupting activity, respectively. The residues of TKIs may represent an environmental hazard; therefore, further ecotoxicological studies focusing also on the effects of their mixtures are warranted.

2019 ◽  
Vol 35 (2) ◽  
pp. 254-267 ◽  
Author(s):  
Christopher L. Souders ◽  
Veronica Perez‐Rodriguez ◽  
Nader El Ahmadie ◽  
Xujia Zhang ◽  
Claire Tischuk ◽  
...  

Toxics ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 16 ◽  
Author(s):  
Sabrina Schiwy ◽  
Ann-Kathrin Herber ◽  
Henner Hollert ◽  
Markus Brinkmann

In the fish embryo toxicity (FET) test with zebrafish (Danio rerio) embryos, 3,4-dichloroaniline (3,4-DCA) is often employed as a positive control substance. Previous studies have characterized bioconcentration and transformation of 3,4-DCA in this test under flow-through conditions. However, the dynamic changes of chemical concentrations in exposure media and embryos were not studied systematically under the commonly used semi-static exposure conditions in multiwell plates. To overcome these limitations, we conducted semi-static exposures experiments where embryolarval zebrafish were exposed to 0.5, 2.0, and 4.0 mg L−1 of 3,4-DCA for up to 120 hpf, with 24-h renewal intervals. During each renewal interval, concentrations of 3,4-DCA were quantified in water samples at 0, 6, 18, and 24 h using high-performance liquid chromatography with diode array detection. Levels of 3,4-DCA in larvae were measured after 120 h exposure. Concentrations of 3,4-DCA in the test vessels decreased rapidly during exposure. Taking these dynamics into account, bioconcentration factors in the present study ranged from 12.9 to 29.8 L kg−1, depending on exposure concentration. In summary, this study contributed to our knowledge of chemical dynamics in the FET test with embryolarval zebrafish, which will aid in defining suitable exposure conditions for future studies.


2009 ◽  
Vol 23 (7) ◽  
pp. 1436-1442 ◽  
Author(s):  
E. Lammer ◽  
H.G. Kamp ◽  
V. Hisgen ◽  
M. Koch ◽  
D. Reinhard ◽  
...  

2021 ◽  
Author(s):  
Julia Gladysheva ◽  
Evdokia Evnukova ◽  
Ekaterina Kondakova ◽  
Milana Kulakova ◽  
Vladimir Efremov

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