Đelić, Ninoslav

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orcid::0000-0001-6787-9097
  • Đelić, Ninoslav (2)
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Analysis of tiazofurin-induced DNA damage in human whole blood cells using an in vitro comet assay

Topalović, Dijana; Živković, Lada; Đelić, Ninoslav; Bajić, Vladan P.; Spremo-Potparević, Biljana

(2020)

TY  - JOUR
AU  - Topalović, Dijana
AU  - Živković, Lada
AU  - Đelić, Ninoslav
AU  - Bajić, Vladan P.
AU  - Spremo-Potparević, Biljana
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9810
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 utvrđenoda 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 (1µM/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.
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 P. 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 utvrđenoda 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 (1µM/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.",
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. P.,& Spremo-Potparević, B.. (2020). Analysis of tiazofurin-induced DNA damage in human whole blood cells using an in vitro comet assay. in Medicinski časopis, 54(3), 91-95.
https://doi.org/10.5937/mckg54-28798
Topalović D, Živković L, Đelić N, Bajić VP, 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 P., 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 . .

Cordyceps sinensis: Genotoxic Potential in Human Peripheral Blood Cells and Antigenotoxic Properties Against Hydrogen Peroxide by Comet Assay

Vasiljević, Jovana; Živković, Lada; Čabarkapa, Andrea; Bajić, Vladan P.; Đelić, Ninoslav; Spremo-Potparević, Biljana

(2016)

TY  - JOUR
AU  - Vasiljević, Jovana
AU  - Živković, Lada
AU  - Čabarkapa, Andrea
AU  - Bajić, Vladan P.
AU  - Đelić, Ninoslav
AU  - Spremo-Potparević, Biljana
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1311
AB  - Context Cordyceps sinensis (C sinensis) is a well-known, traditional, Chinese medicinal mushroom, valued for its beneficial properties for human health. C sinensis has been reported to have immunomodulatory, anticancer, antiaging, antioxidant and anti-inflammatory activity. Despite potential medicinal benefits, no previously published reports are available about the genotoxicity or antigenotoxicity of C sinensis, as detected by comet assay. Objective The objective of the study was to evaluate both the genotoxic and antigenotoxic potential of an extract of C sinensis (CS extract) in human peripheral blood cells. Design The research team designed a pilot study. Setting The study was conducted at the Center for Biological Research, University of Belgrade, in Belgrade, Serbia. Participants Participants were 6 healthy individuals (2 males and 4 females), between the ages of 20 and 45 y, recruited on a voluntary basis, who provided heparinized, peripheral blood samples. Intervention Four concentrations of the CS extract125 mu g/mL, 250 mu g/mL, 500 mu g/mL, and 1000 mu g/mL-were used in the treatment of tested blood cells from the blood samples. Three independent procedures were performed: (1) a genotoxicity assessment, (2) an antigenotoxicity assessment for pretreatment of human cells with the CS extract prior to their exposure to hydrogen peroxide (H2O2) (ie, an evaluation of the benefits of the CS extract as a preventive agent); and (3) posttreatment of human cells with the CS extract after their exposure to H2O2 (ie, an evaluation of the benefits of the CS extract as an interventional agent). Outcome Measures Cells were graded by eye inspection into 5 classes, depending on the extent of DNA damage, representing: (1) class A-undamaged cells with no tail ( LT 5% damaged DNA); (2) class B-low-level damage (5%-20%); (3) class C-medium-level damage (20%-40%); (4) class D-high-level damage (40%-95%), and (5) class E-total destruction ( GT 95%). Results The CS extract proved to be nongenotoxic because no induced DNA damage was detected at all tested concentrations. For the antigenotoxicity assessment of the pretreatment with the CS extract, only the 1000-mu g/mL concentration showed a significant decrease in the number of cells exhibiting H2O2-induced DNA damage. For the posttreatment, the CS extract exhibited antigenotoxic potential by attenuating H2O2-induced DNA damage at all concentrations tested. The evaluation of repair kinetics showed a decrease in DNA-damaged cells 15 min after the application of the CS extract, reaching a maximum potency after 45 min. Conclusions The results indicated that C sinensis can be used as a postapplicative agent that counteracts the effect of oxidative stress. The resulting reduction in DNA damage might be related to its scavenging properties and stimulation of DNA repair.
T2  - Alternative Therapies in Health and Medicine
T1  - Cordyceps sinensis: Genotoxic Potential in Human Peripheral Blood Cells and Antigenotoxic Properties Against Hydrogen Peroxide by Comet Assay
VL  - 22
SP  - 24
EP  - 31
UR  - https://hdl.handle.net/21.15107/rcub_vinar_1311
ER  - 
@article{
author = "Vasiljević, Jovana and Živković, Lada and Čabarkapa, Andrea and Bajić, Vladan P. and Đelić, Ninoslav and Spremo-Potparević, Biljana",
year = "2016",
abstract = "Context Cordyceps sinensis (C sinensis) is a well-known, traditional, Chinese medicinal mushroom, valued for its beneficial properties for human health. C sinensis has been reported to have immunomodulatory, anticancer, antiaging, antioxidant and anti-inflammatory activity. Despite potential medicinal benefits, no previously published reports are available about the genotoxicity or antigenotoxicity of C sinensis, as detected by comet assay. Objective The objective of the study was to evaluate both the genotoxic and antigenotoxic potential of an extract of C sinensis (CS extract) in human peripheral blood cells. Design The research team designed a pilot study. Setting The study was conducted at the Center for Biological Research, University of Belgrade, in Belgrade, Serbia. Participants Participants were 6 healthy individuals (2 males and 4 females), between the ages of 20 and 45 y, recruited on a voluntary basis, who provided heparinized, peripheral blood samples. Intervention Four concentrations of the CS extract125 mu g/mL, 250 mu g/mL, 500 mu g/mL, and 1000 mu g/mL-were used in the treatment of tested blood cells from the blood samples. Three independent procedures were performed: (1) a genotoxicity assessment, (2) an antigenotoxicity assessment for pretreatment of human cells with the CS extract prior to their exposure to hydrogen peroxide (H2O2) (ie, an evaluation of the benefits of the CS extract as a preventive agent); and (3) posttreatment of human cells with the CS extract after their exposure to H2O2 (ie, an evaluation of the benefits of the CS extract as an interventional agent). Outcome Measures Cells were graded by eye inspection into 5 classes, depending on the extent of DNA damage, representing: (1) class A-undamaged cells with no tail ( LT 5% damaged DNA); (2) class B-low-level damage (5%-20%); (3) class C-medium-level damage (20%-40%); (4) class D-high-level damage (40%-95%), and (5) class E-total destruction ( GT 95%). Results The CS extract proved to be nongenotoxic because no induced DNA damage was detected at all tested concentrations. For the antigenotoxicity assessment of the pretreatment with the CS extract, only the 1000-mu g/mL concentration showed a significant decrease in the number of cells exhibiting H2O2-induced DNA damage. For the posttreatment, the CS extract exhibited antigenotoxic potential by attenuating H2O2-induced DNA damage at all concentrations tested. The evaluation of repair kinetics showed a decrease in DNA-damaged cells 15 min after the application of the CS extract, reaching a maximum potency after 45 min. Conclusions The results indicated that C sinensis can be used as a postapplicative agent that counteracts the effect of oxidative stress. The resulting reduction in DNA damage might be related to its scavenging properties and stimulation of DNA repair.",
journal = "Alternative Therapies in Health and Medicine",
title = "Cordyceps sinensis: Genotoxic Potential in Human Peripheral Blood Cells and Antigenotoxic Properties Against Hydrogen Peroxide by Comet Assay",
volume = "22",
pages = "24-31",
url = "https://hdl.handle.net/21.15107/rcub_vinar_1311"
}
Vasiljević, J., Živković, L., Čabarkapa, A., Bajić, V. P., Đelić, N.,& Spremo-Potparević, B.. (2016). Cordyceps sinensis: Genotoxic Potential in Human Peripheral Blood Cells and Antigenotoxic Properties Against Hydrogen Peroxide by Comet Assay. in Alternative Therapies in Health and Medicine, 22, 24-31.
https://hdl.handle.net/21.15107/rcub_vinar_1311
Vasiljević J, Živković L, Čabarkapa A, Bajić VP, Đelić N, Spremo-Potparević B. Cordyceps sinensis: Genotoxic Potential in Human Peripheral Blood Cells and Antigenotoxic Properties Against Hydrogen Peroxide by Comet Assay. in Alternative Therapies in Health and Medicine. 2016;22:24-31.
https://hdl.handle.net/21.15107/rcub_vinar_1311 .
Vasiljević, Jovana, Živković, Lada, Čabarkapa, Andrea, Bajić, Vladan P., Đelić, Ninoslav, Spremo-Potparević, Biljana, "Cordyceps sinensis: Genotoxic Potential in Human Peripheral Blood Cells and Antigenotoxic Properties Against Hydrogen Peroxide by Comet Assay" in Alternative Therapies in Health and Medicine, 22 (2016):24-31,
https://hdl.handle.net/21.15107/rcub_vinar_1311 .
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