Comprehensive insight into the neurotoxic mechanisms of low dose Pb exposure in Wistar rats: Benchmark dose analysis
Само за регистроване кориснике
2022
Аутори
Javorac, DraganaAnđelković, Milena
Repić, Aleksandra
Tatović, Simona
Buha-Đorđević, Aleksandra
Antonijević-Miljaković, Evica
Batinić, Bojan
Boričić, Novica
Đukić-Ćosić, Danijela
Antonijević, Biljana
Bulat, Zorica
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Lead (Pb) is a toxic metal that affects almost all human’s system and organs, with the nervous system as the most sensitive. Better understanding of the Pb neurobehavioral effects and neurotoxicity requires realistic study scenarios based on low level exposure. The aim of this study was to determine neurotoxic effects and mechanisms of Pb in six low doses and to establish dose-response relationship for these effects and related Benchmark dose (BMD). Forty-two, male albino Wistar rats were randomized into seven groups, control and Pb-exposed: 0.1, 0.5, 1, 3, 7 and 15 mg Pb/kg body weight/day (oral gavage) for 28 days. Behavioural tests (Elevated plus maze test, Spontaneous locomotor activity test and Novel object recognition test) were conducted in the last week of experiment, in the control, lower (0.5 mg Pb/kg), middle (3 mg Pb/kg) and higher (15 mg Pb/kg) dose groups. The acetylcholinesterase activity, oxidative status and essential elements levels (Cu, Zn, Mn and Fe) were measured i...n brain tissue along with histological analyses. External and internal dose-response analyses were performed using PROASTweb 70.1 software. The results have shown that subacute exposure to very low doses of Pb resulted in memory deficits in rats that was accompanied with acetylcholinesterase enzyme activity decrease. The observed hyperactive behaviour was accompanied by dose-dependent induction of brain oxidative stress and Zn elevation. The histological alterations in Purkinje cells were only detected in the group treated with the highest Pb dose. The lowest BMD considering entire oxidative status was calculated based on total oxidative status (4.5e-06 mg Pb/kg b.w./day). The findings reported in our study may be beneficial in further evaluating the health consequences and human health risk assessment of low-level Pb exposure.
Кључне речи:
Neurotoxicity / Redox status / Dose-response analysis / Essential elements / Low lead levels / Purkinje cellsИзвор:
Chemico-Biological Interactions, 2022, 360Издавач:
- Elsevier Ireland Ltd
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200161 (Универзитет у Београду, Фармацеутски факултет) (RS-MESTD-inst-2020-200161)
Институција/група
PharmacyTY - JOUR AU - Javorac, Dragana AU - Anđelković, Milena AU - Repić, Aleksandra AU - Tatović, Simona AU - Buha-Đorđević, Aleksandra AU - Antonijević-Miljaković, Evica AU - Batinić, Bojan AU - Boričić, Novica AU - Đukić-Ćosić, Danijela AU - Antonijević, Biljana AU - Bulat, Zorica PY - 2022 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4089 AB - Lead (Pb) is a toxic metal that affects almost all human’s system and organs, with the nervous system as the most sensitive. Better understanding of the Pb neurobehavioral effects and neurotoxicity requires realistic study scenarios based on low level exposure. The aim of this study was to determine neurotoxic effects and mechanisms of Pb in six low doses and to establish dose-response relationship for these effects and related Benchmark dose (BMD). Forty-two, male albino Wistar rats were randomized into seven groups, control and Pb-exposed: 0.1, 0.5, 1, 3, 7 and 15 mg Pb/kg body weight/day (oral gavage) for 28 days. Behavioural tests (Elevated plus maze test, Spontaneous locomotor activity test and Novel object recognition test) were conducted in the last week of experiment, in the control, lower (0.5 mg Pb/kg), middle (3 mg Pb/kg) and higher (15 mg Pb/kg) dose groups. The acetylcholinesterase activity, oxidative status and essential elements levels (Cu, Zn, Mn and Fe) were measured in brain tissue along with histological analyses. External and internal dose-response analyses were performed using PROASTweb 70.1 software. The results have shown that subacute exposure to very low doses of Pb resulted in memory deficits in rats that was accompanied with acetylcholinesterase enzyme activity decrease. The observed hyperactive behaviour was accompanied by dose-dependent induction of brain oxidative stress and Zn elevation. The histological alterations in Purkinje cells were only detected in the group treated with the highest Pb dose. The lowest BMD considering entire oxidative status was calculated based on total oxidative status (4.5e-06 mg Pb/kg b.w./day). The findings reported in our study may be beneficial in further evaluating the health consequences and human health risk assessment of low-level Pb exposure. PB - Elsevier Ireland Ltd T2 - Chemico-Biological Interactions T1 - Comprehensive insight into the neurotoxic mechanisms of low dose Pb exposure in Wistar rats: Benchmark dose analysis VL - 360 DO - 10.1016/j.cbi.2022.109932 ER -
@article{ author = "Javorac, Dragana and Anđelković, Milena and Repić, Aleksandra and Tatović, Simona and Buha-Đorđević, Aleksandra and Antonijević-Miljaković, Evica and Batinić, Bojan and Boričić, Novica and Đukić-Ćosić, Danijela and Antonijević, Biljana and Bulat, Zorica", year = "2022", abstract = "Lead (Pb) is a toxic metal that affects almost all human’s system and organs, with the nervous system as the most sensitive. Better understanding of the Pb neurobehavioral effects and neurotoxicity requires realistic study scenarios based on low level exposure. The aim of this study was to determine neurotoxic effects and mechanisms of Pb in six low doses and to establish dose-response relationship for these effects and related Benchmark dose (BMD). Forty-two, male albino Wistar rats were randomized into seven groups, control and Pb-exposed: 0.1, 0.5, 1, 3, 7 and 15 mg Pb/kg body weight/day (oral gavage) for 28 days. Behavioural tests (Elevated plus maze test, Spontaneous locomotor activity test and Novel object recognition test) were conducted in the last week of experiment, in the control, lower (0.5 mg Pb/kg), middle (3 mg Pb/kg) and higher (15 mg Pb/kg) dose groups. The acetylcholinesterase activity, oxidative status and essential elements levels (Cu, Zn, Mn and Fe) were measured in brain tissue along with histological analyses. External and internal dose-response analyses were performed using PROASTweb 70.1 software. The results have shown that subacute exposure to very low doses of Pb resulted in memory deficits in rats that was accompanied with acetylcholinesterase enzyme activity decrease. The observed hyperactive behaviour was accompanied by dose-dependent induction of brain oxidative stress and Zn elevation. The histological alterations in Purkinje cells were only detected in the group treated with the highest Pb dose. The lowest BMD considering entire oxidative status was calculated based on total oxidative status (4.5e-06 mg Pb/kg b.w./day). The findings reported in our study may be beneficial in further evaluating the health consequences and human health risk assessment of low-level Pb exposure.", publisher = "Elsevier Ireland Ltd", journal = "Chemico-Biological Interactions", title = "Comprehensive insight into the neurotoxic mechanisms of low dose Pb exposure in Wistar rats: Benchmark dose analysis", volume = "360", doi = "10.1016/j.cbi.2022.109932" }
Javorac, D., Anđelković, M., Repić, A., Tatović, S., Buha-Đorđević, A., Antonijević-Miljaković, E., Batinić, B., Boričić, N., Đukić-Ćosić, D., Antonijević, B.,& Bulat, Z.. (2022). Comprehensive insight into the neurotoxic mechanisms of low dose Pb exposure in Wistar rats: Benchmark dose analysis. in Chemico-Biological Interactions Elsevier Ireland Ltd., 360. https://doi.org/10.1016/j.cbi.2022.109932
Javorac D, Anđelković M, Repić A, Tatović S, Buha-Đorđević A, Antonijević-Miljaković E, Batinić B, Boričić N, Đukić-Ćosić D, Antonijević B, Bulat Z. Comprehensive insight into the neurotoxic mechanisms of low dose Pb exposure in Wistar rats: Benchmark dose analysis. in Chemico-Biological Interactions. 2022;360. doi:10.1016/j.cbi.2022.109932 .
Javorac, Dragana, Anđelković, Milena, Repić, Aleksandra, Tatović, Simona, Buha-Đorđević, Aleksandra, Antonijević-Miljaković, Evica, Batinić, Bojan, Boričić, Novica, Đukić-Ćosić, Danijela, Antonijević, Biljana, Bulat, Zorica, "Comprehensive insight into the neurotoxic mechanisms of low dose Pb exposure in Wistar rats: Benchmark dose analysis" in Chemico-Biological Interactions, 360 (2022), https://doi.org/10.1016/j.cbi.2022.109932 . .