The hepatotoxic potential of a mixture of toluene, styrene and ethanol: in silico toxicogenomic data-mining
Hepatotoksični potencijal smeše toluena, stirena i etanola: in silico toksikogenomička analiza
Аутори
Umićević, NinaBaralić, Katarina
Đukić-Ćosić, Danijela
Antonijević-Miljaković, Evica
Buha-Đorđević, Aleksandra
Ćurčić, Marijana
Bulat, Zorica
Antonijević, Biljana
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Organic solvents are still widely used in various industries and considered the most
common chemicals associated with liver injury in workers. For research into the
relationships between these chemicals and genes, interactions among chemicals, molecular
pathways and biological processes, a significant place in toxicity testing has been taken by in
silico methodologies. This study aims to provide evidence for the involvement of a selected
mixture of organic solvents (toluene, styrene, ethanol) in liver disease development and
show the potential of in silico toxicogenomic data-mining in determining possible
mechanisms of mixture toxicity. The Comparative Toxicogenomics Database (CTD),
GeneMania and ToppGene Suite were used for data-mining. The results showed that there
were 17 genes connected with liver injury common for all the tested solvents. Co-expression
(61.73%) was the most prominent interaction between the genes, while physical
interactions were present at 14.56%, co-l...ocalization at 12.54% and interactions predicted by
the server at 6.62%. Gene ontology analysis revealed biological processes affected by the
investigated mixture (reactive oxygen species metabolic and biosynthetic process, response
to oxidative stress, and response to organic cyclic compound). Oxidative stress response,
antioxidant and oxidoreductase activity, vitamin B12 metabolism were noted as the key
molecular pathways contributing to liver disease development. Our results emphasize the
role of oxidative stress as one of the mechanisms of organic solvents' mixture toxicity and
provide new insights into molecular mechanisms involved in hepatotoxicity.
Organski rastvarači se još uvek široko koriste u raznim industrijama i smatraju se
najčešćim hemikalijama povezanim sa oštećenjem jetre kod radnika. Za istraživanje odnosa
između ovih hemikalija i gena, interakcija među hemikalijama, molekularnih puteva i
bioloških procesa, značajno mjesto pripada i in silico metodologijama. Cilj ove studije je da
pruži dokaze za povezanost odabrane smeše organskih rastvarača (toluen, stiren, etanol) u
razvoju bolesti jetre, i da pokaže potencijal in silico toksikogenomičke analize podataka u
određivanju mogućih mehanizama toksičnosti smješe. Za prikupljanje podataka korišteni su
Comparative Toxicogenomics Database (CTD), GeneMania i ToppGene Suite. Rezultati ove
analize su pokazali da postoji 17 gena povezanih s oštećenjem jetre zajedničkih za sva tri
navedena rastvarača. Koekspresija (61,73%) bila je najistaknutija interakcija između gena,
dok su fizičke interakcije bile prisutne sa 14,56%, kolokalizacije sa 12,54%, a interakcije
predviđen...e od strane servera sa 6,62%. Analiza ontologije gena izdvojila je biološke procese
na koje utiče ispitivana smeša (metabolički i biosintetski proces reaktivnih kiseonikovih
vrsta, odgovor na oksidativni stres i odgovor na organska ciklična jedinjenja). Odgovor na
oksidativni stres, aktivnost antioksidanata i oksidoreduktaze, i metabolizam vitamina B12 su
navedeni kao ključni molekularni putevi koji dobrinose razvoju bolesti jetre. Rezultati ovog
rada naglašavaju ulogu oksidativnog stresa kao jednog od mehanizama toksičnosti smeše
organskih rastvarača i daju novi uvid u molekularne mehanizme uključene u
hepatotoksičnost.
Извор:
Arhiv za farmaciju, 2022, 72, 4 suplement, S567-S568Издавач:
- Savez farmaceutskih udruženja Srbije (SFUS)
Напомена:
- VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd
Институција/група
PharmacyTY - CONF AU - Umićević, Nina AU - Baralić, Katarina AU - Đukić-Ćosić, Danijela AU - Antonijević-Miljaković, Evica AU - Buha-Đorđević, Aleksandra AU - Ćurčić, Marijana AU - Bulat, Zorica AU - Antonijević, Biljana PY - 2022 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4608 AB - Organic solvents are still widely used in various industries and considered the most common chemicals associated with liver injury in workers. For research into the relationships between these chemicals and genes, interactions among chemicals, molecular pathways and biological processes, a significant place in toxicity testing has been taken by in silico methodologies. This study aims to provide evidence for the involvement of a selected mixture of organic solvents (toluene, styrene, ethanol) in liver disease development and show the potential of in silico toxicogenomic data-mining in determining possible mechanisms of mixture toxicity. The Comparative Toxicogenomics Database (CTD), GeneMania and ToppGene Suite were used for data-mining. The results showed that there were 17 genes connected with liver injury common for all the tested solvents. Co-expression (61.73%) was the most prominent interaction between the genes, while physical interactions were present at 14.56%, co-localization at 12.54% and interactions predicted by the server at 6.62%. Gene ontology analysis revealed biological processes affected by the investigated mixture (reactive oxygen species metabolic and biosynthetic process, response to oxidative stress, and response to organic cyclic compound). Oxidative stress response, antioxidant and oxidoreductase activity, vitamin B12 metabolism were noted as the key molecular pathways contributing to liver disease development. Our results emphasize the role of oxidative stress as one of the mechanisms of organic solvents' mixture toxicity and provide new insights into molecular mechanisms involved in hepatotoxicity. AB - Organski rastvarači se još uvek široko koriste u raznim industrijama i smatraju se najčešćim hemikalijama povezanim sa oštećenjem jetre kod radnika. Za istraživanje odnosa između ovih hemikalija i gena, interakcija među hemikalijama, molekularnih puteva i bioloških procesa, značajno mjesto pripada i in silico metodologijama. Cilj ove studije je da pruži dokaze za povezanost odabrane smeše organskih rastvarača (toluen, stiren, etanol) u razvoju bolesti jetre, i da pokaže potencijal in silico toksikogenomičke analize podataka u određivanju mogućih mehanizama toksičnosti smješe. Za prikupljanje podataka korišteni su Comparative Toxicogenomics Database (CTD), GeneMania i ToppGene Suite. Rezultati ove analize su pokazali da postoji 17 gena povezanih s oštećenjem jetre zajedničkih za sva tri navedena rastvarača. Koekspresija (61,73%) bila je najistaknutija interakcija između gena, dok su fizičke interakcije bile prisutne sa 14,56%, kolokalizacije sa 12,54%, a interakcije predviđene od strane servera sa 6,62%. Analiza ontologije gena izdvojila je biološke procese na koje utiče ispitivana smeša (metabolički i biosintetski proces reaktivnih kiseonikovih vrsta, odgovor na oksidativni stres i odgovor na organska ciklična jedinjenja). Odgovor na oksidativni stres, aktivnost antioksidanata i oksidoreduktaze, i metabolizam vitamina B12 su navedeni kao ključni molekularni putevi koji dobrinose razvoju bolesti jetre. Rezultati ovog rada naglašavaju ulogu oksidativnog stresa kao jednog od mehanizama toksičnosti smeše organskih rastvarača i daju novi uvid u molekularne mehanizme uključene u hepatotoksičnost. PB - Savez farmaceutskih udruženja Srbije (SFUS) C3 - Arhiv za farmaciju T1 - The hepatotoxic potential of a mixture of toluene, styrene and ethanol: in silico toxicogenomic data-mining T1 - Hepatotoksični potencijal smeše toluena, stirena i etanola: in silico toksikogenomička analiza VL - 72 IS - 4 suplement SP - S567 EP - S568 UR - https://hdl.handle.net/21.15107/rcub_farfar_4608 ER -
@conference{ author = "Umićević, Nina and Baralić, Katarina and Đukić-Ćosić, Danijela and Antonijević-Miljaković, Evica and Buha-Đorđević, Aleksandra and Ćurčić, Marijana and Bulat, Zorica and Antonijević, Biljana", year = "2022", abstract = "Organic solvents are still widely used in various industries and considered the most common chemicals associated with liver injury in workers. For research into the relationships between these chemicals and genes, interactions among chemicals, molecular pathways and biological processes, a significant place in toxicity testing has been taken by in silico methodologies. This study aims to provide evidence for the involvement of a selected mixture of organic solvents (toluene, styrene, ethanol) in liver disease development and show the potential of in silico toxicogenomic data-mining in determining possible mechanisms of mixture toxicity. The Comparative Toxicogenomics Database (CTD), GeneMania and ToppGene Suite were used for data-mining. The results showed that there were 17 genes connected with liver injury common for all the tested solvents. Co-expression (61.73%) was the most prominent interaction between the genes, while physical interactions were present at 14.56%, co-localization at 12.54% and interactions predicted by the server at 6.62%. Gene ontology analysis revealed biological processes affected by the investigated mixture (reactive oxygen species metabolic and biosynthetic process, response to oxidative stress, and response to organic cyclic compound). Oxidative stress response, antioxidant and oxidoreductase activity, vitamin B12 metabolism were noted as the key molecular pathways contributing to liver disease development. Our results emphasize the role of oxidative stress as one of the mechanisms of organic solvents' mixture toxicity and provide new insights into molecular mechanisms involved in hepatotoxicity., Organski rastvarači se još uvek široko koriste u raznim industrijama i smatraju se najčešćim hemikalijama povezanim sa oštećenjem jetre kod radnika. Za istraživanje odnosa između ovih hemikalija i gena, interakcija među hemikalijama, molekularnih puteva i bioloških procesa, značajno mjesto pripada i in silico metodologijama. Cilj ove studije je da pruži dokaze za povezanost odabrane smeše organskih rastvarača (toluen, stiren, etanol) u razvoju bolesti jetre, i da pokaže potencijal in silico toksikogenomičke analize podataka u određivanju mogućih mehanizama toksičnosti smješe. Za prikupljanje podataka korišteni su Comparative Toxicogenomics Database (CTD), GeneMania i ToppGene Suite. Rezultati ove analize su pokazali da postoji 17 gena povezanih s oštećenjem jetre zajedničkih za sva tri navedena rastvarača. Koekspresija (61,73%) bila je najistaknutija interakcija između gena, dok su fizičke interakcije bile prisutne sa 14,56%, kolokalizacije sa 12,54%, a interakcije predviđene od strane servera sa 6,62%. Analiza ontologije gena izdvojila je biološke procese na koje utiče ispitivana smeša (metabolički i biosintetski proces reaktivnih kiseonikovih vrsta, odgovor na oksidativni stres i odgovor na organska ciklična jedinjenja). Odgovor na oksidativni stres, aktivnost antioksidanata i oksidoreduktaze, i metabolizam vitamina B12 su navedeni kao ključni molekularni putevi koji dobrinose razvoju bolesti jetre. Rezultati ovog rada naglašavaju ulogu oksidativnog stresa kao jednog od mehanizama toksičnosti smeše organskih rastvarača i daju novi uvid u molekularne mehanizme uključene u hepatotoksičnost.", publisher = "Savez farmaceutskih udruženja Srbije (SFUS)", journal = "Arhiv za farmaciju", title = "The hepatotoxic potential of a mixture of toluene, styrene and ethanol: in silico toxicogenomic data-mining, Hepatotoksični potencijal smeše toluena, stirena i etanola: in silico toksikogenomička analiza", volume = "72", number = "4 suplement", pages = "S567-S568", url = "https://hdl.handle.net/21.15107/rcub_farfar_4608" }
Umićević, N., Baralić, K., Đukić-Ćosić, D., Antonijević-Miljaković, E., Buha-Đorđević, A., Ćurčić, M., Bulat, Z.,& Antonijević, B.. (2022). The hepatotoxic potential of a mixture of toluene, styrene and ethanol: in silico toxicogenomic data-mining. in Arhiv za farmaciju Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S567-S568. https://hdl.handle.net/21.15107/rcub_farfar_4608
Umićević N, Baralić K, Đukić-Ćosić D, Antonijević-Miljaković E, Buha-Đorđević A, Ćurčić M, Bulat Z, Antonijević B. The hepatotoxic potential of a mixture of toluene, styrene and ethanol: in silico toxicogenomic data-mining. in Arhiv za farmaciju. 2022;72(4 suplement):S567-S568. https://hdl.handle.net/21.15107/rcub_farfar_4608 .
Umićević, Nina, Baralić, Katarina, Đukić-Ćosić, Danijela, Antonijević-Miljaković, Evica, Buha-Đorđević, Aleksandra, Ćurčić, Marijana, Bulat, Zorica, Antonijević, Biljana, "The hepatotoxic potential of a mixture of toluene, styrene and ethanol: in silico toxicogenomic data-mining" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S567-S568, https://hdl.handle.net/21.15107/rcub_farfar_4608 .