Lethal and Sub-Lethal Effects and Modulation of Gene Expression Induced by T Kinase Inhibitors in Zebrafish (Danio Rerio) Embryos
Abstract
:1. Introduction
2. Materials and Methods
2.1. Consumption of Tyrosine Kinase Inhibitors in Slovenia
2.2. Test Substances
2.3. Maintenance of Zebrafish
2.4. TKIs Solutions
2.5. Fish Embryo Toxicity Test (FET)
2.6. Gene Expression Analysis
2.7. Statistical Evaluations
3. Results and Discussion
3.1. Consumption of TKIs in Slovenia
3.2. Fish Embryo Toxicity Test
3.3. Modulation of Gene Expression
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compound | Kinase Target |
---|---|
Imatinib mesylate | BCR-ABL, PDGFR, c-KIT |
Erlotinib | EGFR |
Nilotinib | BCR-ABL, PDGFR, DDR1 |
Sorafenib | VEGFR2, PDGFR, KIT, FLT3, BRAF |
Dasatinib | BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, PDGFRβ |
Regorafenib | VEGFR, PDGFR, BRAF, RAF-1, KIT, Ret, TIE-2, FGFR |
Gene | REGO | DASA | IMAT | |||
---|---|---|---|---|---|---|
Symbol | 0.2 mg/L | 0.6 mg/L | 0.2 mg/L | 0.6 mg/L | 2.3 mg/L | 210 mg/L |
tg | 1.67 ± 0.18* | 2.09 ± 0.67 * | 1.26 ± 0.37 | 0.74 ± 0.18 | 0.72 ± 0.01 * | 1.27 ± 0.33 |
tshb | 0.99 ± 0.12 | 0.92 ± 0.13 | 1.02 ± 0.13 | 0.98 ± 0.18 | 0.95 ± 0.07 | 1.16 ± 0.19 |
thrb | 0.99 ± 0.12 | 0.85 ± 0.14 | 0.91 ± 0.12 | 0.88 ± 0.08 | 0.94 ± 0.09 | 0.98 ± 0.16 |
thraa | 1.05 ± 0.08 | 0.98 ± 0.12 | 1.00 ± 0.07 | 0.91 ± 0.12 | 0.86 ± 0.14 | 0.92 ± 0.08 |
dio2 | 0.95 ± 0.13 | 0.69 ± 0.15 * | 1.05 ± 0.23 | 1.11 ± 0.06 | 0.94 ± 0.19 | 0.74 ± 0.18 |
cyp51 | 1.14 ± 0.36 | 2.35 ± 0.43 * | 1.07 ± 0.39 | 1.13 ± 0.18 | 1.17 ± 0.05 | 1.75 ± 0.30 * |
cyp19a1b | 4.43 ± 1.06 * | 4.35 ± 1.17 * | 0.96 ± 0.30 | 1.65 ± 0.67 | 1.78 ± 0.73 | 2.36 ± 0.55 * |
hsd3b | 2.21 ± 0.67 * | 2.04 ± 1.04 * | 1.89 ± 0.39 * | 0.66 ± 0.03 * | 0.58 ± 0.13 * | 1.21 ± 0.35 |
hsd17b3 | 1.06 ± 0.39 | 1.15 ± 0.21 | 1.07 ± 0.43 | 0.89± 0.08 | 1.31 ± 0.65 | 1.32 ± 0.20 |
esr2b | 1.09 ± 0.03 | 0.89 ± 0.15 | 1.07 ± 0.43 | 0.98 ± 0.08 | 1.07 ± 0.29 | 1.16 ± 0.30 |
esr1 | 0.52 ± 0.02 * | 0.38 ± 0.07 * | 0.68 ± 0.10 | 0.63 ± 0.16 * | 0.66 ± 0.15 | 0.65 ± 0.20 |
apoeb | 0.86 ± 0.34 | 1.13 ± 0.52 | 1.13 ± 0.41 | 0.82 ± 0.16 | 0.94 ± 0.06 | 0.96 ± 0.30 |
gadd45 | 1.53 ± 0.31 * | 0.95 ± 0.37 | 1.14 ± 0.42 | 1.10 ± 0.52 | 0.86 ± 0.05 | 1.01 ± 0.10 |
mcm6 | 0.86 ± 0.14 | 0.64 ± 0.11 * | 0.96 ± 0.11 | 0.89 ± 0.07 | 0.78 ± 0.17 | 0.78 ± 0.05 |
dnajb9 | 0.89 ± 0.11 | 0.74 ± 0.02 | 0.97 ± 0.03 | 0.84 ± 0.06 | 1.05 ± 0.15 | 1.03 ± 0.10 |
bcl2 | 0.95 ± 0.18 | 1.52 ± 0.20 * | 1.02 ± 0.03 | 0.72 ± 0.05 * | 0.95 ± 0.14 | 0.90 ± 0.17 |
pax2a | 1.19 ± 0.39 | 1.09 ± 0.37 | 1.03 ± 0.45 | 0.73 ± 0.001 | 0.95 ± 0.29 | 1.13 ± 0.20 |
slc35 | 0.87 ± 0.20 | 0.69 ± 0.13 | 1.05 ± 0.05 | 0.86 ± 0.08 | 0.77 ± 0.18 | 0.67 ± 0.10 |
nkx1 | 1.01 ± 0.07 | 0.73 ± 0.05 | 1.00 ± 0.11 | 0.96 ± 0.15 | 0.80 ± 0.17 | 0.95 ± 0.32 |
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Elersek, T.; Novak, M.; Mlinar, M.; Virant, I.; Bahor, N.; Leben, K.; Žegura, B.; Filipič, M. Lethal and Sub-Lethal Effects and Modulation of Gene Expression Induced by T Kinase Inhibitors in Zebrafish (Danio Rerio) Embryos. Toxics 2022, 10, 4. https://doi.org/10.3390/toxics10010004
Elersek T, Novak M, Mlinar M, Virant I, Bahor N, Leben K, Žegura B, Filipič M. Lethal and Sub-Lethal Effects and Modulation of Gene Expression Induced by T Kinase Inhibitors in Zebrafish (Danio Rerio) Embryos. Toxics. 2022; 10(1):4. https://doi.org/10.3390/toxics10010004
Chicago/Turabian StyleElersek, Tina, Matjaž Novak, Mateja Mlinar, Igor Virant, Nika Bahor, Karin Leben, Bojana Žegura, and Metka Filipič. 2022. "Lethal and Sub-Lethal Effects and Modulation of Gene Expression Induced by T Kinase Inhibitors in Zebrafish (Danio Rerio) Embryos" Toxics 10, no. 1: 4. https://doi.org/10.3390/toxics10010004
APA StyleElersek, T., Novak, M., Mlinar, M., Virant, I., Bahor, N., Leben, K., Žegura, B., & Filipič, M. (2022). Lethal and Sub-Lethal Effects and Modulation of Gene Expression Induced by T Kinase Inhibitors in Zebrafish (Danio Rerio) Embryos. Toxics, 10(1), 4. https://doi.org/10.3390/toxics10010004