TY  - 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 . .

TY  - JOUR
AU  - Panieri, Emiliano
AU  - Baralić, Katarina
AU  - Đukić-Ćosić, Danijela
AU  - Buha-Đorđević, Aleksandra
AU  - Saso, Luciano
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4354
AB  - Per- and polyfluoroalkyl substances (PFAS) are a group of over 4700 heterogeneous compounds with amphipathic properties and exceptional stability to chemical and thermal degradation. The unique properties of PFAS compounds has been exploited for almost 60 years and has largely contributed to their wide applicability over a vast range of industrial, professional and non-professional uses. However, increasing evidence indicate that these compounds represent also a serious concern for both wildlife and human health as a result of their ubiquitous distribution, their extreme persistence and their bioaccumulative potential. In light of the adverse effects that have been already documented in biota and human populations or that might occur in absence of prompt interventions, the competent authorities in matter of health and environment protection, the industries as well as scientists are cooperating to identify the most appropriate regulatory measures, substitution plans and remediation technologies to mitigate PFAS impacts. In this review, starting from PFAS chemistry, uses and environmental fate, we summarize the current knowledge on PFAS occurrence in different environmental media and their effects on living organisms, with a particular emphasis on humans. Also, we describe present and provisional legislative measures in the European Union framework strategy to regulate PFAS manufacture, import and use as well as some of the most promising treatment technologies designed to remediate PFAS contamination in different environmental compartments.
PB  - MDPI
T2  - Toxics
T1  - PFAS Molecules: A Major Concern for the Human Health and the Environment
VL  - 10
IS  - 2
DO  - 10.3390/toxics10020044
ER  - 

@article{
author = "Panieri, Emiliano and Baralić, Katarina and Đukić-Ćosić, Danijela and Buha-Đorđević, Aleksandra and Saso, Luciano",
year = "2022",
abstract = "Per- and polyfluoroalkyl substances (PFAS) are a group of over 4700 heterogeneous compounds with amphipathic properties and exceptional stability to chemical and thermal degradation. The unique properties of PFAS compounds has been exploited for almost 60 years and has largely contributed to their wide applicability over a vast range of industrial, professional and non-professional uses. However, increasing evidence indicate that these compounds represent also a serious concern for both wildlife and human health as a result of their ubiquitous distribution, their extreme persistence and their bioaccumulative potential. In light of the adverse effects that have been already documented in biota and human populations or that might occur in absence of prompt interventions, the competent authorities in matter of health and environment protection, the industries as well as scientists are cooperating to identify the most appropriate regulatory measures, substitution plans and remediation technologies to mitigate PFAS impacts. In this review, starting from PFAS chemistry, uses and environmental fate, we summarize the current knowledge on PFAS occurrence in different environmental media and their effects on living organisms, with a particular emphasis on humans. Also, we describe present and provisional legislative measures in the European Union framework strategy to regulate PFAS manufacture, import and use as well as some of the most promising treatment technologies designed to remediate PFAS contamination in different environmental compartments.",
publisher = "MDPI",
journal = "Toxics",
title = "PFAS Molecules: A Major Concern for the Human Health and the Environment",
volume = "10",
number = "2",
doi = "10.3390/toxics10020044"
}

Panieri, E., Baralić, K., Đukić-Ćosić, D., Buha-Đorđević, A.,& Saso, L.. (2022). PFAS Molecules: A Major Concern for the Human Health and the Environment. in Toxics
MDPI., 10(2).
https://doi.org/10.3390/toxics10020044

Panieri E, Baralić K, Đukić-Ćosić D, Buha-Đorđević A, Saso L. PFAS Molecules: A Major Concern for the Human Health and the Environment. in Toxics. 2022;10(2).
doi:10.3390/toxics10020044 .

Panieri, Emiliano, Baralić, Katarina, Đukić-Ćosić, Danijela, Buha-Đorđević, Aleksandra, Saso, Luciano, "PFAS Molecules: A Major Concern for the Human Health and the Environment" in Toxics, 10, no. 2 (2022),
https://doi.org/10.3390/toxics10020044 . .

TY  - JOUR
AU  - Buha, Aleksandra
AU  - Baralić, Katarina
AU  - Đukić-Ćosić, Danijela
AU  - Bulat, Zorica
AU  - Tinkov, Alexey
AU  - Panieri, Emiliano
AU  - Saso, Luciano
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3824
AB  - Nuclear factor erythroid 2-related factor 2 (Nrf2), an emerging regulator of cellular resis-tance to oxidants, serves as one of the key defensive factors against a range of pathological processessuch as oxidative damage, carcinogenesis, as well as various harmful chemicals, including metals.An increase in human exposure to toxic metals via air, food, and water has been recently observed,which is mainly due to anthropogenic activities. The relationship between environmental exposureto heavy metals, particularly cadmium (Cd), lead (Pb), mercury (Hg), and nickel (Ni), as well asmetaloid arsenic (As), and transition metal chromium (Cr), and the development of various humandiseases has been extensively investigated.  Their ability to induce reactive oxygen species (ROS)production through direct and indirect actions and cause oxidative stress has been documentedin various organs.  Taking into account that Nrf2 signaling represents an important pathway inmaintaining antioxidant balance, recent research indicates that it can play a dual role depending onthe specific biological context. On one side, Nrf2 represents a potential crucial protective mechanismin metal-induced toxicity, but on the other hand, it can also be a trigger of metal-induced carcinogen-esis under conditions of prolonged exposure and continuous activation. Thus, this review aims tosummarize the state-of-the-art knowledge regarding the functional interrelation between the toxicmetals and Nrf2 signaling.
PB  - MDPI AG
T2  - Antioxidants
T1  - The role of toxic metals and metalloids in nrf2 signaling
VL  - 10
IS  - 5
DO  - 10.3390/antiox10050630
ER  - 

@article{
author = "Buha, Aleksandra and Baralić, Katarina and Đukić-Ćosić, Danijela and Bulat, Zorica and Tinkov, Alexey and Panieri, Emiliano and Saso, Luciano",
year = "2021",
abstract = "Nuclear factor erythroid 2-related factor 2 (Nrf2), an emerging regulator of cellular resis-tance to oxidants, serves as one of the key defensive factors against a range of pathological processessuch as oxidative damage, carcinogenesis, as well as various harmful chemicals, including metals.An increase in human exposure to toxic metals via air, food, and water has been recently observed,which is mainly due to anthropogenic activities. The relationship between environmental exposureto heavy metals, particularly cadmium (Cd), lead (Pb), mercury (Hg), and nickel (Ni), as well asmetaloid arsenic (As), and transition metal chromium (Cr), and the development of various humandiseases has been extensively investigated.  Their ability to induce reactive oxygen species (ROS)production through direct and indirect actions and cause oxidative stress has been documentedin various organs.  Taking into account that Nrf2 signaling represents an important pathway inmaintaining antioxidant balance, recent research indicates that it can play a dual role depending onthe specific biological context. On one side, Nrf2 represents a potential crucial protective mechanismin metal-induced toxicity, but on the other hand, it can also be a trigger of metal-induced carcinogen-esis under conditions of prolonged exposure and continuous activation. Thus, this review aims tosummarize the state-of-the-art knowledge regarding the functional interrelation between the toxicmetals and Nrf2 signaling.",
publisher = "MDPI AG",
journal = "Antioxidants",
title = "The role of toxic metals and metalloids in nrf2 signaling",
volume = "10",
number = "5",
doi = "10.3390/antiox10050630"
}

Buha, A., Baralić, K., Đukić-Ćosić, D., Bulat, Z., Tinkov, A., Panieri, E.,& Saso, L.. (2021). The role of toxic metals and metalloids in nrf2 signaling. in Antioxidants
MDPI AG., 10(5).
https://doi.org/10.3390/antiox10050630

Buha A, Baralić K, Đukić-Ćosić D, Bulat Z, Tinkov A, Panieri E, Saso L. The role of toxic metals and metalloids in nrf2 signaling. in Antioxidants. 2021;10(5).
doi:10.3390/antiox10050630 .

Buha, Aleksandra, Baralić, Katarina, Đukić-Ćosić, Danijela, Bulat, Zorica, Tinkov, Alexey, Panieri, Emiliano, Saso, Luciano, "The role of toxic metals and metalloids in nrf2 signaling" in Antioxidants, 10, no. 5 (2021),
https://doi.org/10.3390/antiox10050630 . .

TY  - JOUR
AU  - Panieri, Emiliano
AU  - Buha, Aleksandra
AU  - Telkoparan-Akillilar, Pelin
AU  - Cevik, Dilek
AU  - Kouretas, Demetrios
AU  - Veskoukis, Aristidis
AU  - Skaperda, Zoi
AU  - Tsatsakis, Aristidis
AU  - Wallace, David
AU  - Suzen, Sibel
AU  - Saso, Luciano
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3551
AB  - The nuclear factor erythroid 2-related factor 2 (NRF2)–Kelch-like ECH-associated protein 1 (KEAP1) regulatory pathway plays an essential role in protecting cells and tissues from oxidative, electrophilic, and xenobiotic stress. By controlling the transactivation of over 500 cytoprotective genes, the NRF2 transcription factor has been implicated in the physiopathology of several human diseases, including cancer. In this respect, accumulating evidence indicates that NRF2 can act as a double-edged sword, being able to mediate tumor suppressive or pro-oncogenic functions, depending on the specific biological context of its activation. Thus, a better understanding of the mechanisms that control NRF2 functions and the most appropriate context of its activation is a prerequisite for the development of effective therapeutic strategies based on NRF2 modulation. In line of principle, the controlled activation of NRF2 might reduce the risk of cancer initiation and development in normal cells by scavenging reactive-oxygen species (ROS) and by preventing genomic instability through decreased DNA damage. In contrast however, already transformed cells with constitutive or prolonged activation of NRF2 signaling might represent a major clinical hurdle and exhibit an aggressive phenotype characterized by therapy resistance and unfavorable prognosis, requiring the use of NRF2 inhibitors. In this review, we will focus on the dual roles of the NRF2-KEAP1 pathway in cancer promotion and inhibition, describing the mechanisms of its activation and potential therapeutic strategies based on the use of context-specific modulation of NRF2.
PB  - MDPI
T2  - Antioxidants
T1  - Potential applications of NRF2 modulators in cancer therapy
VL  - 9
IS  - 3
DO  - 10.3390/antiox9030193
ER  - 

@article{
author = "Panieri, Emiliano and Buha, Aleksandra and Telkoparan-Akillilar, Pelin and Cevik, Dilek and Kouretas, Demetrios and Veskoukis, Aristidis and Skaperda, Zoi and Tsatsakis, Aristidis and Wallace, David and Suzen, Sibel and Saso, Luciano",
year = "2020",
abstract = "The nuclear factor erythroid 2-related factor 2 (NRF2)–Kelch-like ECH-associated protein 1 (KEAP1) regulatory pathway plays an essential role in protecting cells and tissues from oxidative, electrophilic, and xenobiotic stress. By controlling the transactivation of over 500 cytoprotective genes, the NRF2 transcription factor has been implicated in the physiopathology of several human diseases, including cancer. In this respect, accumulating evidence indicates that NRF2 can act as a double-edged sword, being able to mediate tumor suppressive or pro-oncogenic functions, depending on the specific biological context of its activation. Thus, a better understanding of the mechanisms that control NRF2 functions and the most appropriate context of its activation is a prerequisite for the development of effective therapeutic strategies based on NRF2 modulation. In line of principle, the controlled activation of NRF2 might reduce the risk of cancer initiation and development in normal cells by scavenging reactive-oxygen species (ROS) and by preventing genomic instability through decreased DNA damage. In contrast however, already transformed cells with constitutive or prolonged activation of NRF2 signaling might represent a major clinical hurdle and exhibit an aggressive phenotype characterized by therapy resistance and unfavorable prognosis, requiring the use of NRF2 inhibitors. In this review, we will focus on the dual roles of the NRF2-KEAP1 pathway in cancer promotion and inhibition, describing the mechanisms of its activation and potential therapeutic strategies based on the use of context-specific modulation of NRF2.",
publisher = "MDPI",
journal = "Antioxidants",
title = "Potential applications of NRF2 modulators in cancer therapy",
volume = "9",
number = "3",
doi = "10.3390/antiox9030193"
}

Panieri, E., Buha, A., Telkoparan-Akillilar, P., Cevik, D., Kouretas, D., Veskoukis, A., Skaperda, Z., Tsatsakis, A., Wallace, D., Suzen, S.,& Saso, L.. (2020). Potential applications of NRF2 modulators in cancer therapy. in Antioxidants
MDPI., 9(3).
https://doi.org/10.3390/antiox9030193

Panieri E, Buha A, Telkoparan-Akillilar P, Cevik D, Kouretas D, Veskoukis A, Skaperda Z, Tsatsakis A, Wallace D, Suzen S, Saso L. Potential applications of NRF2 modulators in cancer therapy. in Antioxidants. 2020;9(3).
doi:10.3390/antiox9030193 .

Panieri, Emiliano, Buha, Aleksandra, Telkoparan-Akillilar, Pelin, Cevik, Dilek, Kouretas, Demetrios, Veskoukis, Aristidis, Skaperda, Zoi, Tsatsakis, Aristidis, Wallace, David, Suzen, Sibel, Saso, Luciano, "Potential applications of NRF2 modulators in cancer therapy" in Antioxidants, 9, no. 3 (2020),
https://doi.org/10.3390/antiox9030193 . .