TY  - JOUR
AU  - Bruić, Marija
AU  - Pirković, Andrea
AU  - Borozan, Sunčica
AU  - Nacka Aleksić, Mirjana
AU  - Jovanović Krivokuća, Milica
AU  - Spremo-Potparević, Biljana
PY  - 2024
UR  - https://vet-erinar.vet.bg.ac.rs/handle/123456789/3864
AB  - Oxidative stress has been implicated in numerous pregnancy-related disorders. Biologically active plant secondary metabolites, which are present in everyday diet, could prove effective therapeutic agents in preventing
these disorders. This study evaluated effects of taxifolin (dihydroquercetin) on ROS production, markers of
oxidative damage to lipids and proteins, activity of antioxidant enzymes and production of pro-inflammatory
cytokines in H2O2-induced oxidative stress in trophoblast HTR-8/SVneo cells. Taxifolin in 10 µM and 100 µM
concentrations attenuated oxidative damage to lipids and proteins, as evidenced by a decrease in MDA content,
extracellular LDH activity, carbonyl groups and nitrite contents. A reduction in the activity of antioxidant enzymes SOD, CAT and GPx in cells pre-treated with taxifolin, prior to H2O2 exposure, was also observed, along
with a reduction in intracellular ROS production. Both evaluated concentrations of taxifolin showed antiinflammatory activity in trophoblast cells, by reducing production of pro-inflammatory cytokines IL-1β and IL6. In this model of H2O2-induced oxidative stress, taxifolin showed marked antioxidative and antiinflammatory activities in trophoblast cells, adding further evidence of its protective effects and showing potential as a therapeutic agent in preventing adverse pregnancy outcomes.
PB  - Elsevier
T2  - Reproductive Toxicology
T1  - Antioxidative and anti-inflammatory effects of taxifolin in H2O2-induced oxidative stress in HTR-8/SVneo trophoblast cell line
VL  - 126
SP  - 108585
DO  - 10.1016/j.reprotox.2024.108585
ER  - 

@article{
author = "Bruić, Marija and Pirković, Andrea and Borozan, Sunčica and Nacka Aleksić, Mirjana and Jovanović Krivokuća, Milica and Spremo-Potparević, Biljana",
year = "2024",
abstract = "Oxidative stress has been implicated in numerous pregnancy-related disorders. Biologically active plant secondary metabolites, which are present in everyday diet, could prove effective therapeutic agents in preventing
these disorders. This study evaluated effects of taxifolin (dihydroquercetin) on ROS production, markers of
oxidative damage to lipids and proteins, activity of antioxidant enzymes and production of pro-inflammatory
cytokines in H2O2-induced oxidative stress in trophoblast HTR-8/SVneo cells. Taxifolin in 10 µM and 100 µM
concentrations attenuated oxidative damage to lipids and proteins, as evidenced by a decrease in MDA content,
extracellular LDH activity, carbonyl groups and nitrite contents. A reduction in the activity of antioxidant enzymes SOD, CAT and GPx in cells pre-treated with taxifolin, prior to H2O2 exposure, was also observed, along
with a reduction in intracellular ROS production. Both evaluated concentrations of taxifolin showed antiinflammatory activity in trophoblast cells, by reducing production of pro-inflammatory cytokines IL-1β and IL6. In this model of H2O2-induced oxidative stress, taxifolin showed marked antioxidative and antiinflammatory activities in trophoblast cells, adding further evidence of its protective effects and showing potential as a therapeutic agent in preventing adverse pregnancy outcomes.",
publisher = "Elsevier",
journal = "Reproductive Toxicology",
title = "Antioxidative and anti-inflammatory effects of taxifolin in H2O2-induced oxidative stress in HTR-8/SVneo trophoblast cell line",
volume = "126",
pages = "108585",
doi = "10.1016/j.reprotox.2024.108585"
}

Bruić, M., Pirković, A., Borozan, S., Nacka Aleksić, M., Jovanović Krivokuća, M.,& Spremo-Potparević, B.. (2024). Antioxidative and anti-inflammatory effects of taxifolin in H2O2-induced oxidative stress in HTR-8/SVneo trophoblast cell line. in Reproductive Toxicology
Elsevier., 126, 108585.
https://doi.org/10.1016/j.reprotox.2024.108585

Bruić M, Pirković A, Borozan S, Nacka Aleksić M, Jovanović Krivokuća M, Spremo-Potparević B. Antioxidative and anti-inflammatory effects of taxifolin in H2O2-induced oxidative stress in HTR-8/SVneo trophoblast cell line. in Reproductive Toxicology. 2024;126:108585.
doi:10.1016/j.reprotox.2024.108585 .

Bruić, Marija, Pirković, Andrea, Borozan, Sunčica, Nacka Aleksić, Mirjana, Jovanović Krivokuća, Milica, Spremo-Potparević, Biljana, "Antioxidative and anti-inflammatory effects of taxifolin in H2O2-induced oxidative stress in HTR-8/SVneo trophoblast cell line" in Reproductive Toxicology, 126 (2024):108585,
https://doi.org/10.1016/j.reprotox.2024.108585 . .

TY  - JOUR
AU  - Popović, Kosana
AU  - Antonijević Nikolić, Mirjana
AU  - Dražić, Branka
AU  - Jovanović, Dragoljub
AU  - Tanasković, Sladjana
PY  - 2022
UR  - https://vet-erinar.vet.bg.ac.rs/handle/123456789/2622
AB  - Chemical components of teas have received great interest because they are related to health. In this work, data
on the determination of foreign matter, loss on drying/water content, total ash and ash insoluble in hydrochloric
acid are presented. The content of seven heavy metals including Cu, Fe, Mn, Zn, Ni, Cd and Pb were determined
by atomic absorption spectrometry in samples of several herbal teas: Matricariae flos, Thymi herba,
Menthae piperitae folium, Betulae folium, Quercus cortex, Gentianae radix, Frangulae cortex, Althaeae radix,
Uvae ursi folium and Glycyrrhizae radix collected from Šabac’s market, Serbia. The sample preparation
procedure involved dry digestion and dissolution of the ash in 6M HCl and then in 0.1 M HNO
3
. Herbal teas
showed the concentration of heavy metals Cu, Fe, Mn, Zn and Ni in the range: 2.9   0.1 – 22.2   0.9 mg/kg,
118.5   1.1 – 755.5   2.5 mg/kg, 19.0   5.8 – 561.0   1.9 mg/kg, 6.5   0.4 – 242.5   1.4 mg/kg and
2.5   0.1 – 10   1.1 mg/kg, respectively. The level of copper in all samples was uniform. The highest content
of Fe was in Thymi herba, while Mn and Zn were at maximum in Betulae folium. The levels of toxic heavy
metals Cd and Pb were below the detection limit. The obtained values were compared with data available from
literature. The herbal tea samples analyzed contained essential heavy metals (Cu, Fe, Mn, Zn) and probably
essential in trace (Ni), and could obey the daily dietary requirements. Noncancer health risk assessment detected
that the herbal teas of Betulae folium and Frangulae cortex can manifest some health risk to consumers
PB  - Springer Science+Business Media, LLC
T2  - Pharmaceutical Chemistry Journal
T1  - Assessment of the quality of herbal teas from Šabac, Serbia in terms of the content of heavy metals
VL  - 56
IS  - 6
SP  - 827
EP  - 837
DO  - 10.1007/s11094-022-02716-w
ER  - 

@article{
author = "Popović, Kosana and Antonijević Nikolić, Mirjana and Dražić, Branka and Jovanović, Dragoljub and Tanasković, Sladjana",
year = "2022",
abstract = "Chemical components of teas have received great interest because they are related to health. In this work, data
on the determination of foreign matter, loss on drying/water content, total ash and ash insoluble in hydrochloric
acid are presented. The content of seven heavy metals including Cu, Fe, Mn, Zn, Ni, Cd and Pb were determined
by atomic absorption spectrometry in samples of several herbal teas: Matricariae flos, Thymi herba,
Menthae piperitae folium, Betulae folium, Quercus cortex, Gentianae radix, Frangulae cortex, Althaeae radix,
Uvae ursi folium and Glycyrrhizae radix collected from Šabac’s market, Serbia. The sample preparation
procedure involved dry digestion and dissolution of the ash in 6M HCl and then in 0.1 M HNO
3
. Herbal teas
showed the concentration of heavy metals Cu, Fe, Mn, Zn and Ni in the range: 2.9   0.1 – 22.2   0.9 mg/kg,
118.5   1.1 – 755.5   2.5 mg/kg, 19.0   5.8 – 561.0   1.9 mg/kg, 6.5   0.4 – 242.5   1.4 mg/kg and
2.5   0.1 – 10   1.1 mg/kg, respectively. The level of copper in all samples was uniform. The highest content
of Fe was in Thymi herba, while Mn and Zn were at maximum in Betulae folium. The levels of toxic heavy
metals Cd and Pb were below the detection limit. The obtained values were compared with data available from
literature. The herbal tea samples analyzed contained essential heavy metals (Cu, Fe, Mn, Zn) and probably
essential in trace (Ni), and could obey the daily dietary requirements. Noncancer health risk assessment detected
that the herbal teas of Betulae folium and Frangulae cortex can manifest some health risk to consumers",
publisher = "Springer Science+Business Media, LLC",
journal = "Pharmaceutical Chemistry Journal",
title = "Assessment of the quality of herbal teas from Šabac, Serbia in terms of the content of heavy metals",
volume = "56",
number = "6",
pages = "827-837",
doi = "10.1007/s11094-022-02716-w"
}

Popović, K., Antonijević Nikolić, M., Dražić, B., Jovanović, D.,& Tanasković, S.. (2022). Assessment of the quality of herbal teas from Šabac, Serbia in terms of the content of heavy metals. in Pharmaceutical Chemistry Journal
Springer Science+Business Media, LLC., 56(6), 827-837.
https://doi.org/10.1007/s11094-022-02716-w

Popović K, Antonijević Nikolić M, Dražić B, Jovanović D, Tanasković S. Assessment of the quality of herbal teas from Šabac, Serbia in terms of the content of heavy metals. in Pharmaceutical Chemistry Journal. 2022;56(6):827-837.
doi:10.1007/s11094-022-02716-w .

Popović, Kosana, Antonijević Nikolić, Mirjana, Dražić, Branka, Jovanović, Dragoljub, Tanasković, Sladjana, "Assessment of the quality of herbal teas from Šabac, Serbia in terms of the content of heavy metals" in Pharmaceutical Chemistry Journal, 56, no. 6 (2022):827-837,
https://doi.org/10.1007/s11094-022-02716-w . .

TY  - JOUR
AU  - Stevanovic, Strahinja
AU  - Marjanović, Đorđe
AU  - Trailović, Saša M.
AU  - Zdravković, Nemanja
AU  - Perdih, Andrej
AU  - Nikolic, Katarina
PY  - 2021
UR  - https://vet-erinar.vet.bg.ac.rs/handle/123456789/2016
AB  - Parasitic infections are a widespread health problem and research of novel anthelmintic compounds is of the utmost importance. In this study we performed a virtual screening campaign by coupling ligand-based pharmacophore, homology modeling and molecular docking. The virtual screening campaign was conducted using a joined pool of the Drugbank database and a library of purchasable compounds in order to identify drug like compounds with similar pharmacological activity. Our aim was to identify compounds with a potential antihelmintic modulatory effect on nicotinic acetylcholine receptors (nAChR). We derived a 3D pharmacophore model based on the chemical features of known Ascaris suum nAChR modulators. To evaluate the in silico predictions, we tested selected hit compounds in contraction assays using somatic muscle flaps of the Ascaris suum neuromuscular tissue. We tested the modulatory effects of GSK575594A, diazepam and flumazenil hit compounds on nematode contractions induced by acetyl choline (ACh). The compound GSK575594A (3 μM) increased the Emax by 21 % with the EC50 dose ratio of 0.96. Diazepam (100 μM) decreased the Emax by 15 % (1.11 g to 0.95 g) with the EC50 ratio of 1.42 (shifted to the left from 11.25 to 7.93). Flumazenil decreased the EC50 value (from 11.22 μM to 4.88 μM) value showing dose ratio of 2.30, and increased the Emax by 4 % (from 1.54 g to 1.59 g). The observed biological activity was rationalized by molecular docking calculations. Docking scores were calculated against several binding sites within the Ascaris suum homology model. We constructed the homology model using the ACR-16 subunit sequence. The compound GSK575594A showed strong affinity for the intersubunit allosteric binding site within the nAChR transmembrane domain. The binding modes of diazepam and flumazenil suggest that these compounds have a comparable affinity for orthosteric and allosteric nAChR binding sites. The selected hit compounds displayed potential for further optimization as lead compounds. Therefore, such compounds may be useful in neutralizing the growing resistance of parasites to drugs, either alone or in combination with existing conventional anthelmintics.
PB  - Elsevier
T2  - Molecular and Biochemical Parasitology
T1  - Potential modulating effect of the Ascaris suum nicotinic acetylcholine receptor (nAChR) by compounds GSK575594A, diazepam and flumazenil discovered by structure-based virtual screening approach
VL  - 242
DO  - 10.1016/j.molbiopara.2021.111350
ER  - 

@article{
author = "Stevanovic, Strahinja and Marjanović, Đorđe and Trailović, Saša M. and Zdravković, Nemanja and Perdih, Andrej and Nikolic, Katarina",
year = "2021",
abstract = "Parasitic infections are a widespread health problem and research of novel anthelmintic compounds is of the utmost importance. In this study we performed a virtual screening campaign by coupling ligand-based pharmacophore, homology modeling and molecular docking. The virtual screening campaign was conducted using a joined pool of the Drugbank database and a library of purchasable compounds in order to identify drug like compounds with similar pharmacological activity. Our aim was to identify compounds with a potential antihelmintic modulatory effect on nicotinic acetylcholine receptors (nAChR). We derived a 3D pharmacophore model based on the chemical features of known Ascaris suum nAChR modulators. To evaluate the in silico predictions, we tested selected hit compounds in contraction assays using somatic muscle flaps of the Ascaris suum neuromuscular tissue. We tested the modulatory effects of GSK575594A, diazepam and flumazenil hit compounds on nematode contractions induced by acetyl choline (ACh). The compound GSK575594A (3 μM) increased the Emax by 21 % with the EC50 dose ratio of 0.96. Diazepam (100 μM) decreased the Emax by 15 % (1.11 g to 0.95 g) with the EC50 ratio of 1.42 (shifted to the left from 11.25 to 7.93). Flumazenil decreased the EC50 value (from 11.22 μM to 4.88 μM) value showing dose ratio of 2.30, and increased the Emax by 4 % (from 1.54 g to 1.59 g). The observed biological activity was rationalized by molecular docking calculations. Docking scores were calculated against several binding sites within the Ascaris suum homology model. We constructed the homology model using the ACR-16 subunit sequence. The compound GSK575594A showed strong affinity for the intersubunit allosteric binding site within the nAChR transmembrane domain. The binding modes of diazepam and flumazenil suggest that these compounds have a comparable affinity for orthosteric and allosteric nAChR binding sites. The selected hit compounds displayed potential for further optimization as lead compounds. Therefore, such compounds may be useful in neutralizing the growing resistance of parasites to drugs, either alone or in combination with existing conventional anthelmintics.",
publisher = "Elsevier",
journal = "Molecular and Biochemical Parasitology",
title = "Potential modulating effect of the Ascaris suum nicotinic acetylcholine receptor (nAChR) by compounds GSK575594A, diazepam and flumazenil discovered by structure-based virtual screening approach",
volume = "242",
doi = "10.1016/j.molbiopara.2021.111350"
}

Stevanovic, S., Marjanović, Đ., Trailović, S. M., Zdravković, N., Perdih, A.,& Nikolic, K.. (2021). Potential modulating effect of the Ascaris suum nicotinic acetylcholine receptor (nAChR) by compounds GSK575594A, diazepam and flumazenil discovered by structure-based virtual screening approach. in Molecular and Biochemical Parasitology
Elsevier., 242.
https://doi.org/10.1016/j.molbiopara.2021.111350

Stevanovic S, Marjanović Đ, Trailović SM, Zdravković N, Perdih A, Nikolic K. Potential modulating effect of the Ascaris suum nicotinic acetylcholine receptor (nAChR) by compounds GSK575594A, diazepam and flumazenil discovered by structure-based virtual screening approach. in Molecular and Biochemical Parasitology. 2021;242.
doi:10.1016/j.molbiopara.2021.111350 .

Stevanovic, Strahinja, Marjanović, Đorđe, Trailović, Saša M., Zdravković, Nemanja, Perdih, Andrej, Nikolic, Katarina, "Potential modulating effect of the Ascaris suum nicotinic acetylcholine receptor (nAChR) by compounds GSK575594A, diazepam and flumazenil discovered by structure-based virtual screening approach" in Molecular and Biochemical Parasitology, 242 (2021),
https://doi.org/10.1016/j.molbiopara.2021.111350 . .

TY  - JOUR
AU  - Topalović, Dijana
AU  - Živković, Lada
AU  - Đelić, Ninoslav
AU  - Bajić, Vladan
AU  - Spremo-Potparević, Biljana
PY  - 2020
UR  - https://vet-erinar.vet.bg.ac.rs/handle/123456789/2050
AB  - Objective. Inosine 5'-monophosphate dehydrogenase (IMPDH) activity in cancer cells is increased. Tiazofurin selectively inhibits the activity of IMPDH, and it has been granted for the treatment of different cancers and new viral diseases. Its widespread use was limited because exposure to tiazofurin under certain circumstances was found to have a higher frequency of severe non-hematologic toxicity. Therefore, the objective of this study was to examine genotoxic action and inducement of DNA damage of tiazofurin using the comet assay. Methods. The ability of tiazofurin to induce DNA damage was evaluated using single-cell gel electrophoresis (SCGE) technique/comet assay. Human whole blood cells were exposed to three final concentrations of tiazofurin (1µM/mL, 2 µM/mL, and 5 µM/mL) for 30 min in vitro. Results. Our results indicate that tiazofurin produced a significant level of DNA damage on whole blood cells after 30 min of exposure vs. control. All tested concentrations were significantly comet-forming, in a concentration-dependent manner. Conclusion. Our investigation on the tiazofurin-treated cells and their relationship to the formation of DNA damage demonstrated that the genotoxic effect was induced after exposure to tiazofurin under described conditions.
AB  - Cilj. Aktivnost inozin 5’-monofosfat dehidrogenaze
(IMPDH) povećana je u ćelijama karcinoma. Tiazofurin
selektivno inhibira aktivnost IMPDH i odobren je za lečenje
različitih karcinoma i novih virusnih bolesti. Njegova široko
rasprostranjena upotreba bila je ograničena jer je utvrđeno
da je izloženost tiazofurinu pod određenim okolnostima
imala veću incidencu ozbiljne nehematološke toksičnosti.
Stoga je cilj ove studije bio da se pomoću komet testa ispita
genotoksično delovanje i izazivanje DNK oštećenja
tiazofurinom.
Metode. Sposobnost tiazofurina da izazove DNK
oštećenje procenjena je primenom elektroforeze DNK
pojedinačnih ćelija (SCGE) / komet testa. Ćelije pune krvi su
bile izložene trima konačnim koncentracijama tiazofurina (1
µM/mL, 2 µM/mL, and 5 µM/mL) tokom 30 minuta in vitro.
Rezultati. Naši rezultati ukazuju na to da je tiazofurin
proizveo značajan nivo DNK oštećenja na ćelijama pune krvi
nakon 30 minuta izlaganja u odnosu na kontrolu. Sve
ispitivane koncentracije su dovele do značajnog nastanka
kometa, pri čemu je nivo oštećenja rastao s koncentracijom.
Zaključak. Naše istraživanje ćelija tretiranih
tiazofurinom i njihova reakcija na izazivanje DNK oštećenja pokazalo je da je tiazofurin ispoljio genotoksični efekat pod opisanim uslovima
PB  - Kragujevac : Srpsko lekarsko društvo - Okružna podružnica Kragujevac
T2  - Medicinski časopis
T1  - Analysis of tiazofurin-induced DNA damage in human whole blood cells using an in vitro comet assay
T1  - Analiza dnk oštećenja izazvanog tiazofurinom u humanim ćelijama pune krvi primenom in vitro komet testa
VL  - 54
IS  - 3
SP  - 91
EP  - 95
DO  - 10.5937/mckg54-28798
ER  - 

@article{
author = "Topalović, Dijana and Živković, Lada and Đelić, Ninoslav and Bajić, Vladan and Spremo-Potparević, Biljana",
year = "2020",
abstract = "Objective. Inosine 5'-monophosphate dehydrogenase (IMPDH) activity in cancer cells is increased. Tiazofurin selectively inhibits the activity of IMPDH, and it has been granted for the treatment of different cancers and new viral diseases. Its widespread use was limited because exposure to tiazofurin under certain circumstances was found to have a higher frequency of severe non-hematologic toxicity. Therefore, the objective of this study was to examine genotoxic action and inducement of DNA damage of tiazofurin using the comet assay. Methods. The ability of tiazofurin to induce DNA damage was evaluated using single-cell gel electrophoresis (SCGE) technique/comet assay. Human whole blood cells were exposed to three final concentrations of tiazofurin (1µM/mL, 2 µM/mL, and 5 µM/mL) for 30 min in vitro. Results. Our results indicate that tiazofurin produced a significant level of DNA damage on whole blood cells after 30 min of exposure vs. control. All tested concentrations were significantly comet-forming, in a concentration-dependent manner. Conclusion. Our investigation on the tiazofurin-treated cells and their relationship to the formation of DNA damage demonstrated that the genotoxic effect was induced after exposure to tiazofurin under described conditions., Cilj. Aktivnost inozin 5’-monofosfat dehidrogenaze
(IMPDH) povećana je u ćelijama karcinoma. Tiazofurin
selektivno inhibira aktivnost IMPDH i odobren je za lečenje
različitih karcinoma i novih virusnih bolesti. Njegova široko
rasprostranjena upotreba bila je ograničena jer je utvrđeno
da je izloženost tiazofurinu pod određenim okolnostima
imala veću incidencu ozbiljne nehematološke toksičnosti.
Stoga je cilj ove studije bio da se pomoću komet testa ispita
genotoksično delovanje i izazivanje DNK oštećenja
tiazofurinom.
Metode. Sposobnost tiazofurina da izazove DNK
oštećenje procenjena je primenom elektroforeze DNK
pojedinačnih ćelija (SCGE) / komet testa. Ćelije pune krvi su
bile izložene trima konačnim koncentracijama tiazofurina (1
µM/mL, 2 µM/mL, and 5 µM/mL) tokom 30 minuta in vitro.
Rezultati. Naši rezultati ukazuju na to da je tiazofurin
proizveo značajan nivo DNK oštećenja na ćelijama pune krvi
nakon 30 minuta izlaganja u odnosu na kontrolu. Sve
ispitivane koncentracije su dovele do značajnog nastanka
kometa, pri čemu je nivo oštećenja rastao s koncentracijom.
Zaključak. Naše istraživanje ćelija tretiranih
tiazofurinom i njihova reakcija na izazivanje DNK oštećenja pokazalo je da je tiazofurin ispoljio genotoksični efekat pod opisanim uslovima",
publisher = "Kragujevac : Srpsko lekarsko društvo - Okružna podružnica Kragujevac",
journal = "Medicinski časopis",
title = "Analysis of tiazofurin-induced DNA damage in human whole blood cells using an in vitro comet assay, Analiza dnk oštećenja izazvanog tiazofurinom u humanim ćelijama pune krvi primenom in vitro komet testa",
volume = "54",
number = "3",
pages = "91-95",
doi = "10.5937/mckg54-28798"
}

Topalović, D., Živković, L., Đelić, N., Bajić, V.,& Spremo-Potparević, B.. (2020). Analysis of tiazofurin-induced DNA damage in human whole blood cells using an in vitro comet assay. in Medicinski časopis
Kragujevac : Srpsko lekarsko društvo - Okružna podružnica Kragujevac., 54(3), 91-95.
https://doi.org/10.5937/mckg54-28798

Topalović D, Živković L, Đelić N, Bajić V, Spremo-Potparević B. Analysis of tiazofurin-induced DNA damage in human whole blood cells using an in vitro comet assay. in Medicinski časopis. 2020;54(3):91-95.
doi:10.5937/mckg54-28798 .

Topalović, Dijana, Živković, Lada, Đelić, Ninoslav, Bajić, Vladan, Spremo-Potparević, Biljana, "Analysis of tiazofurin-induced DNA damage in human whole blood cells using an in vitro comet assay" in Medicinski časopis, 54, no. 3 (2020):91-95,
https://doi.org/10.5937/mckg54-28798 . .