TY  - JOUR
AU  - Viktorovich Karaulov, Alexander
AU  - Ivanovich Smolyagin, Alexander
AU  - Valeryevna Mikhailova, Irina
AU  - Abramovich Stadnikov, Alexander
AU  - Vyacheslavovna Ermolina, Evgenia
AU  - Vladimirovna Filippova, Yulia
AU  - Aleksandrovna Kuzmicheva, Natalia
AU  - Vlata, Zacharenia
AU  - Buha-Đorđević, Aleksandra
AU  - Tsitsimpikou, Christina
AU  - Hartung, Thomas
AU  - Hernandez, Antonio
AU  - Tsatsakis, Antonio
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3986
AB  - This study assessed the hypothalamic-pituitary-adrenocortical (HPA) axis and lymphoid organs (thymus, spleen, and bone marrow) of Wistar rats treated with a mixture of chromium and benzene. Animals were assessed at three time-points (45, 90 and 135 days) following oral mixture exposure. The hypothalamus-pituitary system was examined in light and electron microscopy. Lymphoid organs underwent a morphological assessment and the immunophenotype of splenocytes was characterized immunohistochemically using monoclonal antibodies. Splenocytes cytokine production of was determined by ELISA after Con-A stimulation. Combined exposure to chromium and benzene in average doses of 20 mg Cr (VI)/kg body weight/day and 0.6 ml benzene/kg body weight/day impaired the responsiveness of the central compartment of the HPA axis, as evidenced by functional activation of the secretory activity of the hypothalamus and pituitary gland, which was not followed by a sufficient extrusion of nonapeptides at the neurohypophysis and hypothalamic median eminence. Chromium and benzene exposure reduced the thymus mass, thymocytes count, and caused a number of structural and functional changes indicative of transient thymus involution. In the spleen, exposure to both chemicals resulted in lymphoreticular hyperplasia and plasma cell-macrophage transformation (also observed in lymph nodes). Apoptosis of thymocytes and lymphocytes was also observed in T-zones of the spleen. Notably, the effects were similar to those observed earlier for the single agents, under the same experimental conditions, without evidence of additivity.
PB  - Academic Press Inc.
T2  - Environmental Research
T1  - Assessment of the combined effects of chromium and benzene on the rat neuroendocrine and immune systems
DO  - 10.1016/j.envres.2021.112096
ER  - 

@article{
author = "Viktorovich Karaulov, Alexander and Ivanovich Smolyagin, Alexander and Valeryevna Mikhailova, Irina and Abramovich Stadnikov, Alexander and Vyacheslavovna Ermolina, Evgenia and Vladimirovna Filippova, Yulia and Aleksandrovna Kuzmicheva, Natalia and Vlata, Zacharenia and Buha-Đorđević, Aleksandra and Tsitsimpikou, Christina and Hartung, Thomas and Hernandez, Antonio and Tsatsakis, Antonio",
year = "2021",
abstract = "This study assessed the hypothalamic-pituitary-adrenocortical (HPA) axis and lymphoid organs (thymus, spleen, and bone marrow) of Wistar rats treated with a mixture of chromium and benzene. Animals were assessed at three time-points (45, 90 and 135 days) following oral mixture exposure. The hypothalamus-pituitary system was examined in light and electron microscopy. Lymphoid organs underwent a morphological assessment and the immunophenotype of splenocytes was characterized immunohistochemically using monoclonal antibodies. Splenocytes cytokine production of was determined by ELISA after Con-A stimulation. Combined exposure to chromium and benzene in average doses of 20 mg Cr (VI)/kg body weight/day and 0.6 ml benzene/kg body weight/day impaired the responsiveness of the central compartment of the HPA axis, as evidenced by functional activation of the secretory activity of the hypothalamus and pituitary gland, which was not followed by a sufficient extrusion of nonapeptides at the neurohypophysis and hypothalamic median eminence. Chromium and benzene exposure reduced the thymus mass, thymocytes count, and caused a number of structural and functional changes indicative of transient thymus involution. In the spleen, exposure to both chemicals resulted in lymphoreticular hyperplasia and plasma cell-macrophage transformation (also observed in lymph nodes). Apoptosis of thymocytes and lymphocytes was also observed in T-zones of the spleen. Notably, the effects were similar to those observed earlier for the single agents, under the same experimental conditions, without evidence of additivity.",
publisher = "Academic Press Inc.",
journal = "Environmental Research",
title = "Assessment of the combined effects of chromium and benzene on the rat neuroendocrine and immune systems",
doi = "10.1016/j.envres.2021.112096"
}

Viktorovich Karaulov, A., Ivanovich Smolyagin, A., Valeryevna Mikhailova, I., Abramovich Stadnikov, A., Vyacheslavovna Ermolina, E., Vladimirovna Filippova, Y., Aleksandrovna Kuzmicheva, N., Vlata, Z., Buha-Đorđević, A., Tsitsimpikou, C., Hartung, T., Hernandez, A.,& Tsatsakis, A.. (2021). Assessment of the combined effects of chromium and benzene on the rat neuroendocrine and immune systems. in Environmental Research
Academic Press Inc...
https://doi.org/10.1016/j.envres.2021.112096

Viktorovich Karaulov A, Ivanovich Smolyagin A, Valeryevna Mikhailova I, Abramovich Stadnikov A, Vyacheslavovna Ermolina E, Vladimirovna Filippova Y, Aleksandrovna Kuzmicheva N, Vlata Z, Buha-Đorđević A, Tsitsimpikou C, Hartung T, Hernandez A, Tsatsakis A. Assessment of the combined effects of chromium and benzene on the rat neuroendocrine and immune systems. in Environmental Research. 2021;.
doi:10.1016/j.envres.2021.112096 .

Viktorovich Karaulov, Alexander, Ivanovich Smolyagin, Alexander, Valeryevna Mikhailova, Irina, Abramovich Stadnikov, Alexander, Vyacheslavovna Ermolina, Evgenia, Vladimirovna Filippova, Yulia, Aleksandrovna Kuzmicheva, Natalia, Vlata, Zacharenia, Buha-Đorđević, Aleksandra, Tsitsimpikou, Christina, Hartung, Thomas, Hernandez, Antonio, Tsatsakis, Antonio, "Assessment of the combined effects of chromium and benzene on the rat neuroendocrine and immune systems" in Environmental Research (2021),
https://doi.org/10.1016/j.envres.2021.112096 . .

TY  - JOUR
AU  - Hernandez, Antonio F.
AU  - Buha, Aleksandra
AU  - Constantin, Carolina
AU  - Wallace, David R.
AU  - Sarigiannis, Dimosthenis
AU  - Neagu, Monica
AU  - Antonijević, Biljana
AU  - Hayes, Wallace A.
AU  - Wilks, Martin F.
AU  - Tsatsakis, Aristidis
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3464
AB  - Humans are exposed to multiple chemicals on a daily basis instead of to just a single chemical, yet the majority of existing toxicity data comes from single-chemical exposure. Multiple factors must be considered such as the route, concentration, duration, and the timing of exposure when determining toxicity to the organism. The need for adequate model systems (in vivo, in vitro, in silico and mathematical) is paramount for better understanding of chemical mixture toxicity. Currently, shortcomings plague each model system as investigators struggle to find the appropriate balance of rigor, reproducibility and appropriateness in mixture toxicity studies. Significant questions exist when comparing single-to mixture-chemical toxicity concerning additivity, synergism, potentiation, or antagonism. Dose/concentration relevance is a major consideration and should be subthreshold for better accuracy in toxicity assessment. Previous work was limited by the technology and methodology of the time, but recent advances have resulted in significant progress in the study of mixture toxicology. Novel technologies have added insight to data obtained from in vivo studies for predictive toxicity testing. These include new in vitro models: omics-related tools, organs-on-a-chip and 3D cell culture, and in silico methods. Taken together, all these modern methodologies improve the understanding of the multiple toxicity pathways associated with adverse outcomes (e.g., adverse outcome pathways), thus allowing investigators to better predict risks linked to exposure to chemical mixtures. As technology and knowledge advance, our ability to harness and integrate separate streams of evidence regarding outcomes associated with chemical mixture exposure improves. As many national and international organizations are currently stressing, studies on chemical mixture toxicity are of primary importance.
PB  - Springer Verlag
T2  - Archives of Toxicology
T1  - Critical assessment and integration of separate lines of evidence for risk assessment of chemical mixtures
VL  - 93
IS  - 10
SP  - 2741
EP  - 2757
DO  - 10.1007/s00204-019-02547-x
ER  - 

@article{
author = "Hernandez, Antonio F. and Buha, Aleksandra and Constantin, Carolina and Wallace, David R. and Sarigiannis, Dimosthenis and Neagu, Monica and Antonijević, Biljana and Hayes, Wallace A. and Wilks, Martin F. and Tsatsakis, Aristidis",
year = "2019",
abstract = "Humans are exposed to multiple chemicals on a daily basis instead of to just a single chemical, yet the majority of existing toxicity data comes from single-chemical exposure. Multiple factors must be considered such as the route, concentration, duration, and the timing of exposure when determining toxicity to the organism. The need for adequate model systems (in vivo, in vitro, in silico and mathematical) is paramount for better understanding of chemical mixture toxicity. Currently, shortcomings plague each model system as investigators struggle to find the appropriate balance of rigor, reproducibility and appropriateness in mixture toxicity studies. Significant questions exist when comparing single-to mixture-chemical toxicity concerning additivity, synergism, potentiation, or antagonism. Dose/concentration relevance is a major consideration and should be subthreshold for better accuracy in toxicity assessment. Previous work was limited by the technology and methodology of the time, but recent advances have resulted in significant progress in the study of mixture toxicology. Novel technologies have added insight to data obtained from in vivo studies for predictive toxicity testing. These include new in vitro models: omics-related tools, organs-on-a-chip and 3D cell culture, and in silico methods. Taken together, all these modern methodologies improve the understanding of the multiple toxicity pathways associated with adverse outcomes (e.g., adverse outcome pathways), thus allowing investigators to better predict risks linked to exposure to chemical mixtures. As technology and knowledge advance, our ability to harness and integrate separate streams of evidence regarding outcomes associated with chemical mixture exposure improves. As many national and international organizations are currently stressing, studies on chemical mixture toxicity are of primary importance.",
publisher = "Springer Verlag",
journal = "Archives of Toxicology",
title = "Critical assessment and integration of separate lines of evidence for risk assessment of chemical mixtures",
volume = "93",
number = "10",
pages = "2741-2757",
doi = "10.1007/s00204-019-02547-x"
}

Hernandez, A. F., Buha, A., Constantin, C., Wallace, D. R., Sarigiannis, D., Neagu, M., Antonijević, B., Hayes, W. A., Wilks, M. F.,& Tsatsakis, A.. (2019). Critical assessment and integration of separate lines of evidence for risk assessment of chemical mixtures. in Archives of Toxicology
Springer Verlag., 93(10), 2741-2757.
https://doi.org/10.1007/s00204-019-02547-x

Hernandez AF, Buha A, Constantin C, Wallace DR, Sarigiannis D, Neagu M, Antonijević B, Hayes WA, Wilks MF, Tsatsakis A. Critical assessment and integration of separate lines of evidence for risk assessment of chemical mixtures. in Archives of Toxicology. 2019;93(10):2741-2757.
doi:10.1007/s00204-019-02547-x .

Hernandez, Antonio F., Buha, Aleksandra, Constantin, Carolina, Wallace, David R., Sarigiannis, Dimosthenis, Neagu, Monica, Antonijević, Biljana, Hayes, Wallace A., Wilks, Martin F., Tsatsakis, Aristidis, "Critical assessment and integration of separate lines of evidence for risk assessment of chemical mixtures" in Archives of Toxicology, 93, no. 10 (2019):2741-2757,
https://doi.org/10.1007/s00204-019-02547-x . .