Hepato-renal toxicity of low dose metal(oid)s mixture in real-life risk simulation in rats: Effects on Nrf2/HO-1 signalling and redox status
Само за регистроване кориснике
2024
Аутори
Vukelić, DraganaBaralić, Katarina
Marić, Đurđica
Đukić-Ćosić, Danijela
Bulat, Zorica
Panieri, Emiliano
Saso, Luciano
Buha-Đorđević, Aleksandra
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
The understanding that humans are exposed to a low level of toxic metals and metalloids in their lifetime has resulted in a shift in scientific and regulatory perspectives from the traditional evaluation of single metal toxicity to complex mixtures, relevant to real-life exposure. Therefore, the aim of this study was to examine the impact of real-life, 90-days exposure to mixture of toxic metal(oid)s, Cd, Pb, Ni, Cr, As and Hg, on the nuclear factor erythroid 2–related factor 2 and hemoxygenase-1 (Nrf2/HO-1) signalling and redox status by assessing total sulfhydryl groups (SH), glutathione (GSH), superoxide dismutase activity (SOD), malondialdehyde (MDA), and ischemia modified albumin (IMA) in the liver and kidney of Wistar rats. Animals (20 males and 20 females) were randomized in 2 control and 6 treated groups that received by oral gavage mixture of metal(oid)s solutions in doses that reflect blood metal(oid) levels determined in previous human biomonitoring study as benchmark dose (...F/M _BMD), median (F/M _MED), and 95th percentile (F/M _95). Our results have shown that metal(oid)s mixture impaired the activation of the Nrf2/HO-1 pathway in the kidney and liver of male rats and kidney of female rats, followed by depletion of GSH levels in males. Additionally, in males elevated levels of IMA in the liver were observed, while in both genders increased MDA levels were observed in the kidney. Interestingly, the effects were more pronounced in male than in female rats. This study is among the first that examined hepato-renal toxic mechanisms of real-life metal mixture exposure, while our results might be of immense importance for assessing the risk of exposure to mixtures of toxic substances.
Кључне речи:
Redox status / Toxic metals / Hemoxygenase-1 / Kidney / Liver / Nuclear factor erythroid 2–related factor 2Извор:
Science of the Total Environment, 2024, 908Издавач:
- Elsevier B.V.
Финансирање / пројекти:
- DecodExpo - Decoding the Role of Exposome in Endocrine Health (RS-ScienceFundRS-Promis-6066532)
DOI: 10.1016/j.scitotenv.2023.168352
ISSN: 0048-9697
PubMed: 37952665
WoS: 001113145100001
Scopus: 2-s2.0-85177730946
Институција/група
PharmacyTY - JOUR AU - Vukelić, Dragana AU - Baralić, Katarina AU - Marić, Đurđica AU - Đukić-Ćosić, Danijela AU - Bulat, Zorica AU - Panieri, Emiliano AU - Saso, Luciano AU - Buha-Đorđević, Aleksandra PY - 2024 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5313 AB - The understanding that humans are exposed to a low level of toxic metals and metalloids in their lifetime has resulted in a shift in scientific and regulatory perspectives from the traditional evaluation of single metal toxicity to complex mixtures, relevant to real-life exposure. Therefore, the aim of this study was to examine the impact of real-life, 90-days exposure to mixture of toxic metal(oid)s, Cd, Pb, Ni, Cr, As and Hg, on the nuclear factor erythroid 2–related factor 2 and hemoxygenase-1 (Nrf2/HO-1) signalling and redox status by assessing total sulfhydryl groups (SH), glutathione (GSH), superoxide dismutase activity (SOD), malondialdehyde (MDA), and ischemia modified albumin (IMA) in the liver and kidney of Wistar rats. Animals (20 males and 20 females) were randomized in 2 control and 6 treated groups that received by oral gavage mixture of metal(oid)s solutions in doses that reflect blood metal(oid) levels determined in previous human biomonitoring study as benchmark dose (F/M _BMD), median (F/M _MED), and 95th percentile (F/M _95). Our results have shown that metal(oid)s mixture impaired the activation of the Nrf2/HO-1 pathway in the kidney and liver of male rats and kidney of female rats, followed by depletion of GSH levels in males. Additionally, in males elevated levels of IMA in the liver were observed, while in both genders increased MDA levels were observed in the kidney. Interestingly, the effects were more pronounced in male than in female rats. This study is among the first that examined hepato-renal toxic mechanisms of real-life metal mixture exposure, while our results might be of immense importance for assessing the risk of exposure to mixtures of toxic substances. PB - Elsevier B.V. T2 - Science of the Total Environment T1 - Hepato-renal toxicity of low dose metal(oid)s mixture in real-life risk simulation in rats: Effects on Nrf2/HO-1 signalling and redox status VL - 908 DO - 10.1016/j.scitotenv.2023.168352 ER -
@article{ author = "Vukelić, Dragana and Baralić, Katarina and Marić, Đurđica and Đukić-Ćosić, Danijela and Bulat, Zorica and Panieri, Emiliano and Saso, Luciano and Buha-Đorđević, Aleksandra", year = "2024", abstract = "The understanding that humans are exposed to a low level of toxic metals and metalloids in their lifetime has resulted in a shift in scientific and regulatory perspectives from the traditional evaluation of single metal toxicity to complex mixtures, relevant to real-life exposure. Therefore, the aim of this study was to examine the impact of real-life, 90-days exposure to mixture of toxic metal(oid)s, Cd, Pb, Ni, Cr, As and Hg, on the nuclear factor erythroid 2–related factor 2 and hemoxygenase-1 (Nrf2/HO-1) signalling and redox status by assessing total sulfhydryl groups (SH), glutathione (GSH), superoxide dismutase activity (SOD), malondialdehyde (MDA), and ischemia modified albumin (IMA) in the liver and kidney of Wistar rats. Animals (20 males and 20 females) were randomized in 2 control and 6 treated groups that received by oral gavage mixture of metal(oid)s solutions in doses that reflect blood metal(oid) levels determined in previous human biomonitoring study as benchmark dose (F/M _BMD), median (F/M _MED), and 95th percentile (F/M _95). Our results have shown that metal(oid)s mixture impaired the activation of the Nrf2/HO-1 pathway in the kidney and liver of male rats and kidney of female rats, followed by depletion of GSH levels in males. Additionally, in males elevated levels of IMA in the liver were observed, while in both genders increased MDA levels were observed in the kidney. Interestingly, the effects were more pronounced in male than in female rats. This study is among the first that examined hepato-renal toxic mechanisms of real-life metal mixture exposure, while our results might be of immense importance for assessing the risk of exposure to mixtures of toxic substances.", publisher = "Elsevier B.V.", journal = "Science of the Total Environment", title = "Hepato-renal toxicity of low dose metal(oid)s mixture in real-life risk simulation in rats: Effects on Nrf2/HO-1 signalling and redox status", volume = "908", doi = "10.1016/j.scitotenv.2023.168352" }
Vukelić, D., Baralić, K., Marić, Đ., Đukić-Ćosić, D., Bulat, Z., Panieri, E., Saso, L.,& Buha-Đorđević, A.. (2024). Hepato-renal toxicity of low dose metal(oid)s mixture in real-life risk simulation in rats: Effects on Nrf2/HO-1 signalling and redox status. in Science of the Total Environment Elsevier B.V.., 908. https://doi.org/10.1016/j.scitotenv.2023.168352
Vukelić D, Baralić K, Marić Đ, Đukić-Ćosić D, Bulat Z, Panieri E, Saso L, Buha-Đorđević A. Hepato-renal toxicity of low dose metal(oid)s mixture in real-life risk simulation in rats: Effects on Nrf2/HO-1 signalling and redox status. in Science of the Total Environment. 2024;908. doi:10.1016/j.scitotenv.2023.168352 .
Vukelić, Dragana, Baralić, Katarina, Marić, Đurđica, Đukić-Ćosić, Danijela, Bulat, Zorica, Panieri, Emiliano, Saso, Luciano, Buha-Đorđević, Aleksandra, "Hepato-renal toxicity of low dose metal(oid)s mixture in real-life risk simulation in rats: Effects on Nrf2/HO-1 signalling and redox status" in Science of the Total Environment, 908 (2024), https://doi.org/10.1016/j.scitotenv.2023.168352 . .