Neurotoxic effects of low dose ranges of environmental metal mixture in a rat model: The benchmark approach
Само за регистроване кориснике
2024
Аутори
Živančević, KatarinaBaralić, Katarina
Vukelić, Dragana
Marić, Đurđica
Kotur-Stevuljević, Jelena
Ivanišević, Jasmina
Savić, Miroslav
Batinić, Bojan
Janković, Radmila
Buha-Đorđević, Aleksandra
Antonijević-Miljaković, Evica
Ćurčić, Marijana
Bulat, Zorica
Antonijević, Biljana
Đukić-Ćosić, Danijela
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Metals exert detrimental effects on various systems within the body, including the nervous system. Nevertheless, the dose-response relationship concerning the administration of low doses of metal mixtures remains inadequately explored. The assessment of neurotoxic effects of lead, cadmium, mercury, and arsenic mixture (MIX) administered at low dose ranges, was conducted using an in vivo approach. A subacute study was conducted on a rat model consisting of a control and five treatment groups subjected to oral exposure with gradually increasing doses (from MIX 1 to MIX 5). The results indicated that behavioural patterns in an already developed nervous system displayed a reduced susceptibility to the metal mixture exposure with tendency of higher doses to alter short term memory. However, the vulnerability of the mature brain to even minimal amounts of the investigated metal mixture was evident, particularly in the context of oxidative stress. Moreover, the study highlights superoxide dis...mutase's sensitivity as an early-stage neurotoxicity marker, as indicated by dose-dependent induction of oxidative stress in the brain revealed through Benchmark analysis. The narrowest Benchmark Dose Interval (BMDI) for superoxide dismutase (SOD) activity (1e-06 - 3.18e-05 mg As/kg b.w./day) indicates that arsenic may dictate the alterations in SOD activity when co-exposed with the other examined metals. The predicted Benchmark doses for oxidative stress parameters were very low, supporting “no-threshold” concept. Histopathological alterations were most severe in the groups treated with higher doses of metal mixture. Similarly, the brain acetylcholinesterase (AChE) activity demonstrated a dose-dependent decrease significant in higher doses, while BMDI suggested Cd as the main contributor in the examined metal mixture. These findings imply varying susceptibility of neurotoxic endpoints to different doses of environmentally relevant metal mixtures, advocating for risk assessment and regulatory measures to address metal pollution and enhance remediation strategies.
Кључне речи:
Low-dose metal mixture / Neurotoxic effects / Oxidative stress / Histopathological changes / Cholinergic susceptibility / Benchmark modelingИзвор:
Environmental Research, 2024, 252, 1, 118680-Издавач:
- Elsevier Inc.
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.envres.2024.118680
ISSN: 0013-9351
PubMed: 38561120
Scopus: 2-s2.0-85190354243
Институција/група
PharmacyTY - JOUR AU - Živančević, Katarina AU - Baralić, Katarina AU - Vukelić, Dragana AU - Marić, Đurđica AU - Kotur-Stevuljević, Jelena AU - Ivanišević, Jasmina AU - Savić, Miroslav AU - Batinić, Bojan AU - Janković, Radmila AU - Buha-Đorđević, Aleksandra AU - Antonijević-Miljaković, Evica AU - Ćurčić, Marijana AU - Bulat, Zorica AU - Antonijević, Biljana AU - Đukić-Ćosić, Danijela PY - 2024 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5614 AB - Metals exert detrimental effects on various systems within the body, including the nervous system. Nevertheless, the dose-response relationship concerning the administration of low doses of metal mixtures remains inadequately explored. The assessment of neurotoxic effects of lead, cadmium, mercury, and arsenic mixture (MIX) administered at low dose ranges, was conducted using an in vivo approach. A subacute study was conducted on a rat model consisting of a control and five treatment groups subjected to oral exposure with gradually increasing doses (from MIX 1 to MIX 5). The results indicated that behavioural patterns in an already developed nervous system displayed a reduced susceptibility to the metal mixture exposure with tendency of higher doses to alter short term memory. However, the vulnerability of the mature brain to even minimal amounts of the investigated metal mixture was evident, particularly in the context of oxidative stress. Moreover, the study highlights superoxide dismutase's sensitivity as an early-stage neurotoxicity marker, as indicated by dose-dependent induction of oxidative stress in the brain revealed through Benchmark analysis. The narrowest Benchmark Dose Interval (BMDI) for superoxide dismutase (SOD) activity (1e-06 - 3.18e-05 mg As/kg b.w./day) indicates that arsenic may dictate the alterations in SOD activity when co-exposed with the other examined metals. The predicted Benchmark doses for oxidative stress parameters were very low, supporting “no-threshold” concept. Histopathological alterations were most severe in the groups treated with higher doses of metal mixture. Similarly, the brain acetylcholinesterase (AChE) activity demonstrated a dose-dependent decrease significant in higher doses, while BMDI suggested Cd as the main contributor in the examined metal mixture. These findings imply varying susceptibility of neurotoxic endpoints to different doses of environmentally relevant metal mixtures, advocating for risk assessment and regulatory measures to address metal pollution and enhance remediation strategies. PB - Elsevier Inc. T2 - Environmental Research T1 - Neurotoxic effects of low dose ranges of environmental metal mixture in a rat model: The benchmark approach VL - 252 IS - 1 SP - 118680 DO - 10.1016/j.envres.2024.118680 ER -
@article{ author = "Živančević, Katarina and Baralić, Katarina and Vukelić, Dragana and Marić, Đurđica and Kotur-Stevuljević, Jelena and Ivanišević, Jasmina and Savić, Miroslav and Batinić, Bojan and Janković, Radmila and Buha-Đorđević, Aleksandra and Antonijević-Miljaković, Evica and Ćurčić, Marijana and Bulat, Zorica and Antonijević, Biljana and Đukić-Ćosić, Danijela", year = "2024", abstract = "Metals exert detrimental effects on various systems within the body, including the nervous system. Nevertheless, the dose-response relationship concerning the administration of low doses of metal mixtures remains inadequately explored. The assessment of neurotoxic effects of lead, cadmium, mercury, and arsenic mixture (MIX) administered at low dose ranges, was conducted using an in vivo approach. A subacute study was conducted on a rat model consisting of a control and five treatment groups subjected to oral exposure with gradually increasing doses (from MIX 1 to MIX 5). The results indicated that behavioural patterns in an already developed nervous system displayed a reduced susceptibility to the metal mixture exposure with tendency of higher doses to alter short term memory. However, the vulnerability of the mature brain to even minimal amounts of the investigated metal mixture was evident, particularly in the context of oxidative stress. Moreover, the study highlights superoxide dismutase's sensitivity as an early-stage neurotoxicity marker, as indicated by dose-dependent induction of oxidative stress in the brain revealed through Benchmark analysis. The narrowest Benchmark Dose Interval (BMDI) for superoxide dismutase (SOD) activity (1e-06 - 3.18e-05 mg As/kg b.w./day) indicates that arsenic may dictate the alterations in SOD activity when co-exposed with the other examined metals. The predicted Benchmark doses for oxidative stress parameters were very low, supporting “no-threshold” concept. Histopathological alterations were most severe in the groups treated with higher doses of metal mixture. Similarly, the brain acetylcholinesterase (AChE) activity demonstrated a dose-dependent decrease significant in higher doses, while BMDI suggested Cd as the main contributor in the examined metal mixture. These findings imply varying susceptibility of neurotoxic endpoints to different doses of environmentally relevant metal mixtures, advocating for risk assessment and regulatory measures to address metal pollution and enhance remediation strategies.", publisher = "Elsevier Inc.", journal = "Environmental Research", title = "Neurotoxic effects of low dose ranges of environmental metal mixture in a rat model: The benchmark approach", volume = "252", number = "1", pages = "118680", doi = "10.1016/j.envres.2024.118680" }
Živančević, K., Baralić, K., Vukelić, D., Marić, Đ., Kotur-Stevuljević, J., Ivanišević, J., Savić, M., Batinić, B., Janković, R., Buha-Đorđević, A., Antonijević-Miljaković, E., Ćurčić, M., Bulat, Z., Antonijević, B.,& Đukić-Ćosić, D.. (2024). Neurotoxic effects of low dose ranges of environmental metal mixture in a rat model: The benchmark approach. in Environmental Research Elsevier Inc.., 252(1), 118680. https://doi.org/10.1016/j.envres.2024.118680
Živančević K, Baralić K, Vukelić D, Marić Đ, Kotur-Stevuljević J, Ivanišević J, Savić M, Batinić B, Janković R, Buha-Đorđević A, Antonijević-Miljaković E, Ćurčić M, Bulat Z, Antonijević B, Đukić-Ćosić D. Neurotoxic effects of low dose ranges of environmental metal mixture in a rat model: The benchmark approach. in Environmental Research. 2024;252(1):118680. doi:10.1016/j.envres.2024.118680 .
Živančević, Katarina, Baralić, Katarina, Vukelić, Dragana, Marić, Đurđica, Kotur-Stevuljević, Jelena, Ivanišević, Jasmina, Savić, Miroslav, Batinić, Bojan, Janković, Radmila, Buha-Đorđević, Aleksandra, Antonijević-Miljaković, Evica, Ćurčić, Marijana, Bulat, Zorica, Antonijević, Biljana, Đukić-Ćosić, Danijela, "Neurotoxic effects of low dose ranges of environmental metal mixture in a rat model: The benchmark approach" in Environmental Research, 252, no. 1 (2024):118680, https://doi.org/10.1016/j.envres.2024.118680 . .