@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"
}