Integrative investigation of hematotoxic effects induced by low doses of lead, cadmium, mercury and arsenic mixture: In vivo and in silico approach
Само за регистроване кориснике
2024
Аутори
Živančević, Katarina![](/themes/MirageFarFaR/images/orcid.png)
Živanović, Jovana
![](/themes/MirageFarFaR/images/orcid.png)
Baralić, Katarina
![](/themes/MirageFarFaR/images/orcid.png)
Božić, Dragica
![](/themes/MirageFarFaR/images/orcid.png)
Marić, Đurđica
![](/themes/MirageFarFaR/images/orcid.png)
Vukelić, Dragana
![](/themes/MirageFarFaR/images/orcid.png)
Antonijević-Miljaković, Evica
![](/themes/MirageFarFaR/images/orcid.png)
Buha-Đorđević, Aleksandra
![](/themes/MirageFarFaR/images/orcid.png)
Ćurčić, Marijana
![](/themes/MirageFarFaR/images/orcid.png)
Bulat, Zorica
![](/themes/MirageFarFaR/images/orcid.png)
Antonijević, Biljana
![](/themes/MirageFarFaR/images/orcid.png)
Đukić-Ćosić, Danijela
![](/themes/MirageFarFaR/images/orcid.png)
Чланак у часопису (Објављена верзија)
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Метаподаци
Приказ свих података о документуАпстракт
The effect of the lead (Pb), cadmium (Cd), mercury (Hg) and arsenic (As) mixture (MIX) on hematotoxicity development was investigated trough combined approach. In vivo subacute study (28 days) was performed on rats (5 per group): a control group and five groups orally exposed to increasing metal(loid) mixture doses, MIX 1- MIX 5 (mg/kg bw./day) (Pb: 0.003, 0.01, 0.1, 0.3, 1; Cd: 0.01, 0.03, 0.3, 0.9, 3; Hg: 0.0002, 0.0006, 0.006, 0.018, 0.06; As: 0.002, 0.006, 0.06, 0.18, 0.6). Blood was taken for analysis of hematological parameters and serum iron (Fe) analysis. MIX treatment increased thrombocyte/platelet count and MCHC and decreased Hb, HCT, MCV and MCH values compared to control, indicating the development of anemia and thrombocytosis. BMDIs with the narrowest width were identified for MCH [pg] (6.030E-03 - 1.287E-01 mg Pb/kg bw./day; 2.010E-02 - 4.290E-01 mg Cd/kg bw./day; 4.020E-04 - 8.580E-03 mg Hg/kg bw./day; 4.020E-03 - 8.580E-02 mg As/kg bw./day). In silico analysis showed ta...rget genes connected with MIX and the development of: anemia - ACHE, GSR, PARP1, TNF; thrombocytosis – JAK2, CALR, MPL, THPO; hematological diseases - FAS and ALAD. The main extracted pathways for anemia were related to apoptosis and oxidative stress; for thrombocytosis were signaling pathways of Jak-STAT and TPO. Changes in miRNAs and transcription factors enabled the mode of action (MoA) development based on the obtained results, contributing to mechanistic understanding and hematological risk related to MIX exposure.
Кључне речи:
Benchmark modelling / Hematotoxicity / Mode of action / Toxic metal(loid)s mixtureИзвор:
Science of the Total Environment, 2024, 930Издавач:
- Elsevier B.V.
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200161 (Универзитет у Београду, Фармацеутски факултет) (RS-MESTD-inst-2020-200161)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200178 (Универзитет у Београду, Биолошки факултет) (RS-MESTD-inst-2020-200178)
DOI: 10.1016/j.scitotenv.2024.172608
ISSN: 0048-9697
PubMed: 38653421
Scopus: 2-s2.0-85191489918
Институција/група
PharmacyTY - JOUR AU - Živančević, Katarina AU - Živanović, Jovana AU - Baralić, Katarina AU - Božić, Dragica AU - Marić, Đurđica AU - Vukelić, Dragana AU - Antonijević-Miljaković, Evica AU - Buha-Đorđević, Aleksandra AU - Ćurčić, Marijana AU - Bulat, Zorica AU - Antonijević, Biljana AU - Đukić-Ćosić, Danijela PY - 2024 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5624 AB - The effect of the lead (Pb), cadmium (Cd), mercury (Hg) and arsenic (As) mixture (MIX) on hematotoxicity development was investigated trough combined approach. In vivo subacute study (28 days) was performed on rats (5 per group): a control group and five groups orally exposed to increasing metal(loid) mixture doses, MIX 1- MIX 5 (mg/kg bw./day) (Pb: 0.003, 0.01, 0.1, 0.3, 1; Cd: 0.01, 0.03, 0.3, 0.9, 3; Hg: 0.0002, 0.0006, 0.006, 0.018, 0.06; As: 0.002, 0.006, 0.06, 0.18, 0.6). Blood was taken for analysis of hematological parameters and serum iron (Fe) analysis. MIX treatment increased thrombocyte/platelet count and MCHC and decreased Hb, HCT, MCV and MCH values compared to control, indicating the development of anemia and thrombocytosis. BMDIs with the narrowest width were identified for MCH [pg] (6.030E-03 - 1.287E-01 mg Pb/kg bw./day; 2.010E-02 - 4.290E-01 mg Cd/kg bw./day; 4.020E-04 - 8.580E-03 mg Hg/kg bw./day; 4.020E-03 - 8.580E-02 mg As/kg bw./day). In silico analysis showed target genes connected with MIX and the development of: anemia - ACHE, GSR, PARP1, TNF; thrombocytosis – JAK2, CALR, MPL, THPO; hematological diseases - FAS and ALAD. The main extracted pathways for anemia were related to apoptosis and oxidative stress; for thrombocytosis were signaling pathways of Jak-STAT and TPO. Changes in miRNAs and transcription factors enabled the mode of action (MoA) development based on the obtained results, contributing to mechanistic understanding and hematological risk related to MIX exposure. PB - Elsevier B.V. T2 - Science of the Total Environment T1 - Integrative investigation of hematotoxic effects induced by low doses of lead, cadmium, mercury and arsenic mixture: In vivo and in silico approach VL - 930 DO - 10.1016/j.scitotenv.2024.172608 DO - 2-s2.0-85191489918 ER -
@article{ author = "Živančević, Katarina and Živanović, Jovana and Baralić, Katarina and Božić, Dragica and Marić, Đurđica and Vukelić, Dragana and Antonijević-Miljaković, Evica and Buha-Đorđević, Aleksandra and Ćurčić, Marijana and Bulat, Zorica and Antonijević, Biljana and Đukić-Ćosić, Danijela", year = "2024", abstract = "The effect of the lead (Pb), cadmium (Cd), mercury (Hg) and arsenic (As) mixture (MIX) on hematotoxicity development was investigated trough combined approach. In vivo subacute study (28 days) was performed on rats (5 per group): a control group and five groups orally exposed to increasing metal(loid) mixture doses, MIX 1- MIX 5 (mg/kg bw./day) (Pb: 0.003, 0.01, 0.1, 0.3, 1; Cd: 0.01, 0.03, 0.3, 0.9, 3; Hg: 0.0002, 0.0006, 0.006, 0.018, 0.06; As: 0.002, 0.006, 0.06, 0.18, 0.6). Blood was taken for analysis of hematological parameters and serum iron (Fe) analysis. MIX treatment increased thrombocyte/platelet count and MCHC and decreased Hb, HCT, MCV and MCH values compared to control, indicating the development of anemia and thrombocytosis. BMDIs with the narrowest width were identified for MCH [pg] (6.030E-03 - 1.287E-01 mg Pb/kg bw./day; 2.010E-02 - 4.290E-01 mg Cd/kg bw./day; 4.020E-04 - 8.580E-03 mg Hg/kg bw./day; 4.020E-03 - 8.580E-02 mg As/kg bw./day). In silico analysis showed target genes connected with MIX and the development of: anemia - ACHE, GSR, PARP1, TNF; thrombocytosis – JAK2, CALR, MPL, THPO; hematological diseases - FAS and ALAD. The main extracted pathways for anemia were related to apoptosis and oxidative stress; for thrombocytosis were signaling pathways of Jak-STAT and TPO. Changes in miRNAs and transcription factors enabled the mode of action (MoA) development based on the obtained results, contributing to mechanistic understanding and hematological risk related to MIX exposure.", publisher = "Elsevier B.V.", journal = "Science of the Total Environment", title = "Integrative investigation of hematotoxic effects induced by low doses of lead, cadmium, mercury and arsenic mixture: In vivo and in silico approach", volume = "930", doi = "10.1016/j.scitotenv.2024.172608, 2-s2.0-85191489918" }
Živančević, K., Živanović, J., Baralić, K., Božić, D., Marić, Đ., Vukelić, D., Antonijević-Miljaković, E., Buha-Đorđević, A., Ćurčić, M., Bulat, Z., Antonijević, B.,& Đukić-Ćosić, D.. (2024). Integrative investigation of hematotoxic effects induced by low doses of lead, cadmium, mercury and arsenic mixture: In vivo and in silico approach. in Science of the Total Environment Elsevier B.V.., 930. https://doi.org/10.1016/j.scitotenv.2024.172608
Živančević K, Živanović J, Baralić K, Božić D, Marić Đ, Vukelić D, Antonijević-Miljaković E, Buha-Đorđević A, Ćurčić M, Bulat Z, Antonijević B, Đukić-Ćosić D. Integrative investigation of hematotoxic effects induced by low doses of lead, cadmium, mercury and arsenic mixture: In vivo and in silico approach. in Science of the Total Environment. 2024;930. doi:10.1016/j.scitotenv.2024.172608 .
Živančević, Katarina, Živanović, Jovana, Baralić, Katarina, Božić, Dragica, Marić, Đurđica, Vukelić, Dragana, Antonijević-Miljaković, Evica, Buha-Đorđević, Aleksandra, Ćurčić, Marijana, Bulat, Zorica, Antonijević, Biljana, Đukić-Ćosić, Danijela, "Integrative investigation of hematotoxic effects induced by low doses of lead, cadmium, mercury and arsenic mixture: In vivo and in silico approach" in Science of the Total Environment, 930 (2024), https://doi.org/10.1016/j.scitotenv.2024.172608 . .