TY  - CONF
AU  - Seke, Mariana
AU  - Petrović, Danijela
AU  - Labudović Borović, Milica
AU  - Jović, Danica
AU  - Borišev, Ivana
AU  - Kanački, Zdenko
AU  - Žikić, Dragan
AU  - Đorđević, Aleksandar
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12680
AB  - Introduction: Doxorubicin is the most prominent chemotherapeutic, but its clinical use is limited by its severe systemic toxicity. An iron overload aggravates anthracycline toxicity. Fullerenol in aqueous solutions is in the form of polyanionic nanoparticles, serving as a good carrier of positively charged ions, such as Fe2+. Fullerenol’s antioxidant activity has already been proved in different biological systems. The aim of our study was to investigate the effects of the fullerenol/iron nanocomposite on the rat liver as a pretreatment to doxorubicin application. Methods: After the 24h-treatment, adult male Wistar rats were sacrificed and livers were collected for ultrastructural and qRT-PCR analysis. Considering the ability of doxorubicin to induce oxidative stress, and the fullerenol’s capability to mitigate it, gene expression of enzymes involved in antioxidant defense was measured. Results: Ultrastructural analysis revealed that liver tissue was mainly preserved after the nanocomposite was applied prior to doxorubicin. However, the hepatocytes of animals treated with doxorubicin, presented significantly damaged morphology. Apoptosis of hepatocytes and endothelial cells, mitochondria of irregular size and with disruption of cristae, diffuse injury of capillaries were observed. RT-PCR results have shown that treatment with doxorubicin alone significantly increase the mRNA levels of catalase (p=0.008) and superoxide-dismutase (p=0.000003), while the pretreatment with the nanocomposite prior the doxirubicine treatment, dramaticly downregulated the mRNA levels of catalase (p=0.0004) and superoxide-dismutase (p=0.0001). Conclusion: Our results suggest that the fullerenol/iron nanocomposite applied as pretreatment to doxorubicin, demonstrated protection to the liver tissue and induced less damage to the hepatocytes in comparison to doxorubicin alone.
PB  - Belgrade : University of Belgrade, Faculty of Biology
C3  - CoMBoS1 - 1st Congress of Molecular Biologists of Serbia with international participation : Book of abstracts
T1  - Fullerenol/iron nanocomposite modulates doxorubicin-induced hepatotoxicity
SP  - 71
EP  - 71
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12680
ER  - 

@conference{
author = "Seke, Mariana and Petrović, Danijela and Labudović Borović, Milica and Jović, Danica and Borišev, Ivana and Kanački, Zdenko and Žikić, Dragan and Đorđević, Aleksandar",
year = "2017",
abstract = "Introduction: Doxorubicin is the most prominent chemotherapeutic, but its clinical use is limited by its severe systemic toxicity. An iron overload aggravates anthracycline toxicity. Fullerenol in aqueous solutions is in the form of polyanionic nanoparticles, serving as a good carrier of positively charged ions, such as Fe2+. Fullerenol’s antioxidant activity has already been proved in different biological systems. The aim of our study was to investigate the effects of the fullerenol/iron nanocomposite on the rat liver as a pretreatment to doxorubicin application. Methods: After the 24h-treatment, adult male Wistar rats were sacrificed and livers were collected for ultrastructural and qRT-PCR analysis. Considering the ability of doxorubicin to induce oxidative stress, and the fullerenol’s capability to mitigate it, gene expression of enzymes involved in antioxidant defense was measured. Results: Ultrastructural analysis revealed that liver tissue was mainly preserved after the nanocomposite was applied prior to doxorubicin. However, the hepatocytes of animals treated with doxorubicin, presented significantly damaged morphology. Apoptosis of hepatocytes and endothelial cells, mitochondria of irregular size and with disruption of cristae, diffuse injury of capillaries were observed. RT-PCR results have shown that treatment with doxorubicin alone significantly increase the mRNA levels of catalase (p=0.008) and superoxide-dismutase (p=0.000003), while the pretreatment with the nanocomposite prior the doxirubicine treatment, dramaticly downregulated the mRNA levels of catalase (p=0.0004) and superoxide-dismutase (p=0.0001). Conclusion: Our results suggest that the fullerenol/iron nanocomposite applied as pretreatment to doxorubicin, demonstrated protection to the liver tissue and induced less damage to the hepatocytes in comparison to doxorubicin alone.",
publisher = "Belgrade : University of Belgrade, Faculty of Biology",
journal = "CoMBoS1 - 1st Congress of Molecular Biologists of Serbia with international participation : Book of abstracts",
title = "Fullerenol/iron nanocomposite modulates doxorubicin-induced hepatotoxicity",
pages = "71-71",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12680"
}

Seke, M., Petrović, D., Labudović Borović, M., Jović, D., Borišev, I., Kanački, Z., Žikić, D.,& Đorđević, A.. (2017). Fullerenol/iron nanocomposite modulates doxorubicin-induced hepatotoxicity. in CoMBoS1 - 1st Congress of Molecular Biologists of Serbia with international participation : Book of abstracts
Belgrade : University of Belgrade, Faculty of Biology., 71-71.
https://hdl.handle.net/21.15107/rcub_vinar_12680

Seke M, Petrović D, Labudović Borović M, Jović D, Borišev I, Kanački Z, Žikić D, Đorđević A. Fullerenol/iron nanocomposite modulates doxorubicin-induced hepatotoxicity. in CoMBoS1 - 1st Congress of Molecular Biologists of Serbia with international participation : Book of abstracts. 2017;:71-71.
https://hdl.handle.net/21.15107/rcub_vinar_12680 .

Seke, Mariana, Petrović, Danijela, Labudović Borović, Milica, Jović, Danica, Borišev, Ivana, Kanački, Zdenko, Žikić, Dragan, Đorđević, Aleksandar, "Fullerenol/iron nanocomposite modulates doxorubicin-induced hepatotoxicity" in CoMBoS1 - 1st Congress of Molecular Biologists of Serbia with international participation : Book of abstracts (2017):71-71,
https://hdl.handle.net/21.15107/rcub_vinar_12680 .

TY  - JOUR
AU  - Seke, Mariana
AU  - Petrović, Danijela
AU  - Đorđević, Aleksandar N.
AU  - Jović, Danica S.
AU  - Labudović-Borović, Milica
AU  - Kanački, Zdenko
AU  - Janković, Milan
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1306
AB  - Fullerenol (C-60(OH)(24)) is present in aqueous solutions in the form of polyanion nanoparticles with particles size distribution within the range from 15 to 42 nm. In this research it is assumed that these features could enable fullerenol nanoparticles (FNPs) to bind positively charged molecules like doxorubicin (DOX) and serve as drug carriers. Considering this, fullerenol/doxorubicin nanocomposite (FNP/DOX) is formed and characterized by ultra-performance liquid chromatography tandem mass spectrometry, dynamic light scattering, atomic force microscopy and transmission electron microscopy. Measurements have shown that DOX did not significantly affect particle size (23 nm). It is also assumed that FNP/DOX could reduce the acute cardiotoxic effects of DOX in vivo (Wistar rats treated i.p.). In this study, quantitative real time polymerase chain reaction results have shown that treatment with DOX alone caused significant increase in mRNA levels of catalase (p LT 0.05) enzyme indicating the presence of oxidative stress. This effect is significantly reduced by the treatment with FNP/DOX (p LT 0.05). Furthermore, mRNA levels of antiapoptotic enzyme (Bcl-2) are significantly increased (p LT 0.05) in all treated groups, particularly where FNP/DOX was applied, suggesting cell resistance to apoptosis. Moreover, ultrastructural analysis has shown the absence of myelin figures within the mitochondria in the heart tissue with FNP/DOX treatment, indicating reduction of oxidative stress. Hence, our results have implied that FNP/DOX is generally less harmful to the heart compared to DOX.
T2  - Nanotechnology
T1  - Fullerenol/doxorubicin nanocomposite mitigates acute oxidative stress and modulates apoptosis in myocardial tissue
VL  - 27
IS  - 48
DO  - 10.1088/0957-4484/27/48/485101
ER  - 

@article{
author = "Seke, Mariana and Petrović, Danijela and Đorđević, Aleksandar N. and Jović, Danica S. and Labudović-Borović, Milica and Kanački, Zdenko and Janković, Milan",
year = "2016",
abstract = "Fullerenol (C-60(OH)(24)) is present in aqueous solutions in the form of polyanion nanoparticles with particles size distribution within the range from 15 to 42 nm. In this research it is assumed that these features could enable fullerenol nanoparticles (FNPs) to bind positively charged molecules like doxorubicin (DOX) and serve as drug carriers. Considering this, fullerenol/doxorubicin nanocomposite (FNP/DOX) is formed and characterized by ultra-performance liquid chromatography tandem mass spectrometry, dynamic light scattering, atomic force microscopy and transmission electron microscopy. Measurements have shown that DOX did not significantly affect particle size (23 nm). It is also assumed that FNP/DOX could reduce the acute cardiotoxic effects of DOX in vivo (Wistar rats treated i.p.). In this study, quantitative real time polymerase chain reaction results have shown that treatment with DOX alone caused significant increase in mRNA levels of catalase (p LT 0.05) enzyme indicating the presence of oxidative stress. This effect is significantly reduced by the treatment with FNP/DOX (p LT 0.05). Furthermore, mRNA levels of antiapoptotic enzyme (Bcl-2) are significantly increased (p LT 0.05) in all treated groups, particularly where FNP/DOX was applied, suggesting cell resistance to apoptosis. Moreover, ultrastructural analysis has shown the absence of myelin figures within the mitochondria in the heart tissue with FNP/DOX treatment, indicating reduction of oxidative stress. Hence, our results have implied that FNP/DOX is generally less harmful to the heart compared to DOX.",
journal = "Nanotechnology",
title = "Fullerenol/doxorubicin nanocomposite mitigates acute oxidative stress and modulates apoptosis in myocardial tissue",
volume = "27",
number = "48",
doi = "10.1088/0957-4484/27/48/485101"
}

Seke, M., Petrović, D., Đorđević, A. N., Jović, D. S., Labudović-Borović, M., Kanački, Z.,& Janković, M.. (2016). Fullerenol/doxorubicin nanocomposite mitigates acute oxidative stress and modulates apoptosis in myocardial tissue. in Nanotechnology, 27(48).
https://doi.org/10.1088/0957-4484/27/48/485101

Seke M, Petrović D, Đorđević AN, Jović DS, Labudović-Borović M, Kanački Z, Janković M. Fullerenol/doxorubicin nanocomposite mitigates acute oxidative stress and modulates apoptosis in myocardial tissue. in Nanotechnology. 2016;27(48).
doi:10.1088/0957-4484/27/48/485101 .

Seke, Mariana, Petrović, Danijela, Đorđević, Aleksandar N., Jović, Danica S., Labudović-Borović, Milica, Kanački, Zdenko, Janković, Milan, "Fullerenol/doxorubicin nanocomposite mitigates acute oxidative stress and modulates apoptosis in myocardial tissue" in Nanotechnology, 27, no. 48 (2016),
https://doi.org/10.1088/0957-4484/27/48/485101 . .

TY  - JOUR
AU  - Labudović-Borović, Milica
AU  - Icevic, Ivana
AU  - Kanački, Zdenko
AU  - Zikic, Dragan
AU  - Seke, Mariana
AU  - Injac, Rade
AU  - Đorđević, Aleksandar N.
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5924
AB  - Cardioprotective effects of fullerenol C-60(OH)(24) nanoparticles (FNP) were investigated in pigs after a single treatment with doxorubicin (DOX). Semithin and ultrathin sections of myocardial tissue routinely prepared for transmission electron microscopy were analyzed. Extensive intracellular damage was confirmed in cardiomyocytes of DOX-treated animals. By means of ultrastructural analysis, a certain degree of parenchymal degeneration was confirmed even in animals treated with FNP alone, including both the oral and the intraperitoneal application of the substance. The cardioprotective effects of FNP in animals previously treated with DOX were recognized to a certain extent, but were not fully confirmed at the ultrastructural level. Nevertheless, the myocardial morphology of DOX-treated animals improved after the admission of FNP. Irregular orientation of myofibrils, myofibrillar disruption, intracellular edema, and vacuolization were reduced, but not completely eliminated. Reduction of these cellular alterations was achieved if FNP was applied orally 6 h prior to DOX treatment in a dose of 18 mg/kg. However, numerous defects, including the inner mitochondrial membrane and the plasma membrane disruption of certain cells persisted. In FNP/DOX-treated animals, the presence of multinuclear cells with mitosis-like figures resembling metaphase or anaphase were observed, indicating that DOX and FNP could have a complex influence on the cell cycle of cardiomyocytes. Based on this experiment, further careful increase in dosage may be advised to enhance FNP-induced cardioprotection. These investigations should, however, always be combined with ultrastructural analysis. The FNP/DOX interaction is an excellent model for the investigation of cardiomyocyte cell death and cell cycle mechanisms.
T2  - Ultrastructural Pathology
T1  - Effects of Fullerenol C-60(OH)(24) Nanoparticles on a Single-dose Doxorubicin-induced Cardiotoxicity in Pigs: An Ultrastructural Study
VL  - 38
IS  - 2
SP  - 150
EP  - 163
DO  - 10.3109/01913123.2013.822045
ER  - 

@article{
author = "Labudović-Borović, Milica and Icevic, Ivana and Kanački, Zdenko and Zikic, Dragan and Seke, Mariana and Injac, Rade and Đorđević, Aleksandar N.",
year = "2014",
abstract = "Cardioprotective effects of fullerenol C-60(OH)(24) nanoparticles (FNP) were investigated in pigs after a single treatment with doxorubicin (DOX). Semithin and ultrathin sections of myocardial tissue routinely prepared for transmission electron microscopy were analyzed. Extensive intracellular damage was confirmed in cardiomyocytes of DOX-treated animals. By means of ultrastructural analysis, a certain degree of parenchymal degeneration was confirmed even in animals treated with FNP alone, including both the oral and the intraperitoneal application of the substance. The cardioprotective effects of FNP in animals previously treated with DOX were recognized to a certain extent, but were not fully confirmed at the ultrastructural level. Nevertheless, the myocardial morphology of DOX-treated animals improved after the admission of FNP. Irregular orientation of myofibrils, myofibrillar disruption, intracellular edema, and vacuolization were reduced, but not completely eliminated. Reduction of these cellular alterations was achieved if FNP was applied orally 6 h prior to DOX treatment in a dose of 18 mg/kg. However, numerous defects, including the inner mitochondrial membrane and the plasma membrane disruption of certain cells persisted. In FNP/DOX-treated animals, the presence of multinuclear cells with mitosis-like figures resembling metaphase or anaphase were observed, indicating that DOX and FNP could have a complex influence on the cell cycle of cardiomyocytes. Based on this experiment, further careful increase in dosage may be advised to enhance FNP-induced cardioprotection. These investigations should, however, always be combined with ultrastructural analysis. The FNP/DOX interaction is an excellent model for the investigation of cardiomyocyte cell death and cell cycle mechanisms.",
journal = "Ultrastructural Pathology",
title = "Effects of Fullerenol C-60(OH)(24) Nanoparticles on a Single-dose Doxorubicin-induced Cardiotoxicity in Pigs: An Ultrastructural Study",
volume = "38",
number = "2",
pages = "150-163",
doi = "10.3109/01913123.2013.822045"
}

Labudović-Borović, M., Icevic, I., Kanački, Z., Zikic, D., Seke, M., Injac, R.,& Đorđević, A. N.. (2014). Effects of Fullerenol C-60(OH)(24) Nanoparticles on a Single-dose Doxorubicin-induced Cardiotoxicity in Pigs: An Ultrastructural Study. in Ultrastructural Pathology, 38(2), 150-163.
https://doi.org/10.3109/01913123.2013.822045

Labudović-Borović M, Icevic I, Kanački Z, Zikic D, Seke M, Injac R, Đorđević AN. Effects of Fullerenol C-60(OH)(24) Nanoparticles on a Single-dose Doxorubicin-induced Cardiotoxicity in Pigs: An Ultrastructural Study. in Ultrastructural Pathology. 2014;38(2):150-163.
doi:10.3109/01913123.2013.822045 .

Labudović-Borović, Milica, Icevic, Ivana, Kanački, Zdenko, Zikic, Dragan, Seke, Mariana, Injac, Rade, Đorđević, Aleksandar N., "Effects of Fullerenol C-60(OH)(24) Nanoparticles on a Single-dose Doxorubicin-induced Cardiotoxicity in Pigs: An Ultrastructural Study" in Ultrastructural Pathology, 38, no. 2 (2014):150-163,
https://doi.org/10.3109/01913123.2013.822045 . .