TY  - JOUR
AU  - Aaseth, Jan
AU  - Javorac, Dragana
AU  - Buha-Đorđević, Aleksandra
AU  - Bulat, Zorica
AU  - Skalny, Anatoly
AU  - Zaitseva, Irina
AU  - Aschner, Michael
AU  - Tinkov, Alexey
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4059
AB  - Persistent organic pollutants (POPs) are considered as potential obesogens that may affect adipose tissue development and functioning, thus promoting obesity. However, various POPs may have different mechanisms of action. The objective of the present review is to discuss the key mechanisms linking exposure to POPs to adipose tissue dysfunction and obesity. Laboratory data clearly demonstrate that the mechanisms associated with the interference of exposure to POPs with obesity include: (a) dysregulation of adipogenesis regulators (PPAR  and C/EBP); (b) affinity and binding to nuclear receptors; (c) epigenetic effects; and/or (d) proinflammatory activity. Although in vivo data are generally corroborative of the in vitro results, studies in living organisms have shown that the impact of POPs on adipogenesis is affected by biological factors such as sex, age, and period of exposure. Epidemiological data demonstrate a significant association between exposure to POPs and obesity and obesity-associated metabolic disturbances (e.g., type 2 diabetes mellitus and metabolic syndrome), although the existing data are considered insufficient. In conclusion, both laboratory and epidemiological data underline the significant role of POPs as environmental obesogens. However, further studies are required to better characterize both the mechanisms and the dose/concentration-response effects of exposure to POPs in the development of obesity and other metabolic diseases.
PB  - MDPI
T2  - Toxics
T1  - The Role of Persistent Organic Pollutants in Obesity: A Review of Laboratory and Epidemiological Studies
VL  - 10
IS  - 2
DO  - 10.3390/toxics10020065
ER  - 

@article{
author = "Aaseth, Jan and Javorac, Dragana and Buha-Đorđević, Aleksandra and Bulat, Zorica and Skalny, Anatoly and Zaitseva, Irina and Aschner, Michael and Tinkov, Alexey",
year = "2022",
abstract = "Persistent organic pollutants (POPs) are considered as potential obesogens that may affect adipose tissue development and functioning, thus promoting obesity. However, various POPs may have different mechanisms of action. The objective of the present review is to discuss the key mechanisms linking exposure to POPs to adipose tissue dysfunction and obesity. Laboratory data clearly demonstrate that the mechanisms associated with the interference of exposure to POPs with obesity include: (a) dysregulation of adipogenesis regulators (PPAR  and C/EBP); (b) affinity and binding to nuclear receptors; (c) epigenetic effects; and/or (d) proinflammatory activity. Although in vivo data are generally corroborative of the in vitro results, studies in living organisms have shown that the impact of POPs on adipogenesis is affected by biological factors such as sex, age, and period of exposure. Epidemiological data demonstrate a significant association between exposure to POPs and obesity and obesity-associated metabolic disturbances (e.g., type 2 diabetes mellitus and metabolic syndrome), although the existing data are considered insufficient. In conclusion, both laboratory and epidemiological data underline the significant role of POPs as environmental obesogens. However, further studies are required to better characterize both the mechanisms and the dose/concentration-response effects of exposure to POPs in the development of obesity and other metabolic diseases.",
publisher = "MDPI",
journal = "Toxics",
title = "The Role of Persistent Organic Pollutants in Obesity: A Review of Laboratory and Epidemiological Studies",
volume = "10",
number = "2",
doi = "10.3390/toxics10020065"
}

Aaseth, J., Javorac, D., Buha-Đorđević, A., Bulat, Z., Skalny, A., Zaitseva, I., Aschner, M.,& Tinkov, A.. (2022). The Role of Persistent Organic Pollutants in Obesity: A Review of Laboratory and Epidemiological Studies. in Toxics
MDPI., 10(2).
https://doi.org/10.3390/toxics10020065

Aaseth J, Javorac D, Buha-Đorđević A, Bulat Z, Skalny A, Zaitseva I, Aschner M, Tinkov A. The Role of Persistent Organic Pollutants in Obesity: A Review of Laboratory and Epidemiological Studies. in Toxics. 2022;10(2).
doi:10.3390/toxics10020065 .

Aaseth, Jan, Javorac, Dragana, Buha-Đorđević, Aleksandra, Bulat, Zorica, Skalny, Anatoly, Zaitseva, Irina, Aschner, Michael, Tinkov, Alexey, "The Role of Persistent Organic Pollutants in Obesity: A Review of Laboratory and Epidemiological Studies" in Toxics, 10, no. 2 (2022),
https://doi.org/10.3390/toxics10020065 . .

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  - Tinkov, Alexey
AU  - Nguyen, Thuy
AU  - Santamaria, Abe
AU  - Bowman, Aaron
AU  - Buha-Đorđević, Aleksandra
AU  - Paoliello, Monica Maria
AU  - Skalny, Anatoly
AU  - Aschner, Michael
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3910
AB  - Metal dyshomeostasis, and especially overexposure, is known to cause adverse health effects due to modulation of a variety of metabolic pathways. An increasing body of literature has demonstrated that metal exposure may affect SIRT signaling, although the existing data are insufficient. Therefore, in this review we discuss the available data (PubMed-Medline, Google Scholar) on the influence of metal overload on sirtuin (SIRT) signaling and its association with other mechanisms involved in metal-induced toxicity. The existing data demonstrate that cadmium (Cd), mercury (Hg), arsenic (As), lead (Pb), aluminium (Al), hexavalent chromium (CrVI), manganese (Mn), iron (Fe), and copper (Cu) can inhibit SIRT1 activity. In addition, an inhibitory effect of Cd, Pb, As, and Fe on SIRT3 has been demonstrated. In turn, metal-induced inhibition of SIRT was shown to affect deacetylation of target proteins including FOXO, PGC1α, p53 and NF-kB. Increased acetylation downregulates PGC1α signaling pathway, resulting in cellular altered redox status and increased susceptibility to oxidative stress, as well as decreased mitochondrial biogenesis. Lower rates of LKB1 deacetylation may be responsible for metal-induced decreases in AMPK activity and subsequent metabolic disturbances. A shift to the acetylated FOXO results in increased expression of pro-apoptotic genes which upregulates apoptosis together with increased p53 signaling. Correspondingly, decreased NF-kB deacetylation results in upregulation of target genes of proinflammatory cytokines, enzymes, and cellular adhesion molecules thus promoting inflammation. Therefore, alterations in sirtuin activity may at least partially mediate metal-induced metabolic disturbances that have been implicated in neurotoxicity, nephrotoxicity, cardiotoxicity, and other toxic effects of heavy metals.
PB  - Springer
T2  - Archives of Toxicology
T1  - Sirtuins as molecular targets, mediators, and protective agents in metal‑induced toxicity
DO  - 10.1007/s00204-021-03048-6
ER  - 

@article{
author = "Tinkov, Alexey and Nguyen, Thuy and Santamaria, Abe and Bowman, Aaron and Buha-Đorđević, Aleksandra and Paoliello, Monica Maria and Skalny, Anatoly and Aschner, Michael",
year = "2021",
abstract = "Metal dyshomeostasis, and especially overexposure, is known to cause adverse health effects due to modulation of a variety of metabolic pathways. An increasing body of literature has demonstrated that metal exposure may affect SIRT signaling, although the existing data are insufficient. Therefore, in this review we discuss the available data (PubMed-Medline, Google Scholar) on the influence of metal overload on sirtuin (SIRT) signaling and its association with other mechanisms involved in metal-induced toxicity. The existing data demonstrate that cadmium (Cd), mercury (Hg), arsenic (As), lead (Pb), aluminium (Al), hexavalent chromium (CrVI), manganese (Mn), iron (Fe), and copper (Cu) can inhibit SIRT1 activity. In addition, an inhibitory effect of Cd, Pb, As, and Fe on SIRT3 has been demonstrated. In turn, metal-induced inhibition of SIRT was shown to affect deacetylation of target proteins including FOXO, PGC1α, p53 and NF-kB. Increased acetylation downregulates PGC1α signaling pathway, resulting in cellular altered redox status and increased susceptibility to oxidative stress, as well as decreased mitochondrial biogenesis. Lower rates of LKB1 deacetylation may be responsible for metal-induced decreases in AMPK activity and subsequent metabolic disturbances. A shift to the acetylated FOXO results in increased expression of pro-apoptotic genes which upregulates apoptosis together with increased p53 signaling. Correspondingly, decreased NF-kB deacetylation results in upregulation of target genes of proinflammatory cytokines, enzymes, and cellular adhesion molecules thus promoting inflammation. Therefore, alterations in sirtuin activity may at least partially mediate metal-induced metabolic disturbances that have been implicated in neurotoxicity, nephrotoxicity, cardiotoxicity, and other toxic effects of heavy metals.",
publisher = "Springer",
journal = "Archives of Toxicology",
title = "Sirtuins as molecular targets, mediators, and protective agents in metal‑induced toxicity",
doi = "10.1007/s00204-021-03048-6"
}

Tinkov, A., Nguyen, T., Santamaria, A., Bowman, A., Buha-Đorđević, A., Paoliello, M. M., Skalny, A.,& Aschner, M.. (2021). Sirtuins as molecular targets, mediators, and protective agents in metal‑induced toxicity. in Archives of Toxicology
Springer..
https://doi.org/10.1007/s00204-021-03048-6

Tinkov A, Nguyen T, Santamaria A, Bowman A, Buha-Đorđević A, Paoliello MM, Skalny A, Aschner M. Sirtuins as molecular targets, mediators, and protective agents in metal‑induced toxicity. in Archives of Toxicology. 2021;.
doi:10.1007/s00204-021-03048-6 .

Tinkov, Alexey, Nguyen, Thuy, Santamaria, Abe, Bowman, Aaron, Buha-Đorđević, Aleksandra, Paoliello, Monica Maria, Skalny, Anatoly, Aschner, Michael, "Sirtuins as molecular targets, mediators, and protective agents in metal‑induced toxicity" in Archives of Toxicology (2021),
https://doi.org/10.1007/s00204-021-03048-6 . .