TY  - CONF
AU  - Tasić, Jelena
AU  - Vidičević Novaković, Sašenka
AU  - Stanojević, Željka
AU  - Paunović, Verica
AU  - Petričević, Saša
AU  - Martinović, Tamara
AU  - Kravić-Stevović, Tamara
AU  - Ćirić, Darko
AU  - Marković, Zoran J.
AU  - Isaković, Aleksandra
AU  - Trajković, Vladimir
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11057
AB  - Background: Experimental autoimmune encephalomyelitis (EAE) is one of the most studied model of neuroinflammation, used to test immunomodulatory and antiinflammatory drugs. Graphene quantum dots (GQD) are oval graphite twodimensional sheets with a diameter <100 nm, one carbon atom thickness, with potential applications in biomedicine. Objective: To investigate the potential protective effect of GQD in EAE model. Methods: Female DA rats were immunized with spinal cord homogenate and Freund’s complete adjuvant. GQD treatment (10 mg/kg, ip) was administrated during the inductive, effector and both phases of a disease. MAP kinase (MAPK) and Akt activity in popliteal lymph nodes (PLN) and CNS was determined by western blot. Quantitative PCR and flow cytometry were used to examine the expression of proinflammatory cytokines and specific transcription factors while infiltration of GQD in cells/tissues was detected by transmission electron microscopy. GQD antiinflamatory/direct cytoprotective effect was analyzed on oligodendrocyte and neuron cell cultures by MTT assay. Data were analized by Mann Whitney test (p<0.05 was considered as statistical significant difference). Results: GQD administration, in all phases of EAE, significantly reduced clinical score of a disease. Clinical improvement correlates with increase in activity of ERK, p38 and Akt that is followed by reduction of Th1 cell response in PLN and infiltrated spinal coard T cells. Due to its capacity to infiltrate cells and tissues, GQD exhibits direct cytoprotective effect on CNS. Additionaly, GQD reduced the expression of proinflammatory cytokines in ConA stimulated lymphocytes. Conclusion: GQD alleviate EAE, through direct cytoprotective effect on CNS and inhibition of Th1 cell response.
PB  - Belgrade : Serbian Neuroscience Society
C3  - 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
T1  - Graphene Quantum Dots show protective effect in animal model of neuroinflammation
SP  - 114
UR  - https://hdl.handle.net/21.15107/rcub_vinar_11057
ER  - 

@conference{
author = "Tasić, Jelena and Vidičević Novaković, Sašenka and Stanojević, Željka and Paunović, Verica and Petričević, Saša and Martinović, Tamara and Kravić-Stevović, Tamara and Ćirić, Darko and Marković, Zoran J. and Isaković, Aleksandra and Trajković, Vladimir",
year = "2023",
abstract = "Background: Experimental autoimmune encephalomyelitis (EAE) is one of the most studied model of neuroinflammation, used to test immunomodulatory and antiinflammatory drugs. Graphene quantum dots (GQD) are oval graphite twodimensional sheets with a diameter <100 nm, one carbon atom thickness, with potential applications in biomedicine. Objective: To investigate the potential protective effect of GQD in EAE model. Methods: Female DA rats were immunized with spinal cord homogenate and Freund’s complete adjuvant. GQD treatment (10 mg/kg, ip) was administrated during the inductive, effector and both phases of a disease. MAP kinase (MAPK) and Akt activity in popliteal lymph nodes (PLN) and CNS was determined by western blot. Quantitative PCR and flow cytometry were used to examine the expression of proinflammatory cytokines and specific transcription factors while infiltration of GQD in cells/tissues was detected by transmission electron microscopy. GQD antiinflamatory/direct cytoprotective effect was analyzed on oligodendrocyte and neuron cell cultures by MTT assay. Data were analized by Mann Whitney test (p<0.05 was considered as statistical significant difference). Results: GQD administration, in all phases of EAE, significantly reduced clinical score of a disease. Clinical improvement correlates with increase in activity of ERK, p38 and Akt that is followed by reduction of Th1 cell response in PLN and infiltrated spinal coard T cells. Due to its capacity to infiltrate cells and tissues, GQD exhibits direct cytoprotective effect on CNS. Additionaly, GQD reduced the expression of proinflammatory cytokines in ConA stimulated lymphocytes. Conclusion: GQD alleviate EAE, through direct cytoprotective effect on CNS and inhibition of Th1 cell response.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade",
title = "Graphene Quantum Dots show protective effect in animal model of neuroinflammation",
pages = "114",
url = "https://hdl.handle.net/21.15107/rcub_vinar_11057"
}

Tasić, J., Vidičević Novaković, S., Stanojević, Ž., Paunović, V., Petričević, S., Martinović, T., Kravić-Stevović, T., Ćirić, D., Marković, Z. J., Isaković, A.,& Trajković, V.. (2023). Graphene Quantum Dots show protective effect in animal model of neuroinflammation. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
Belgrade : Serbian Neuroscience Society., 114.
https://hdl.handle.net/21.15107/rcub_vinar_11057

Tasić J, Vidičević Novaković S, Stanojević Ž, Paunović V, Petričević S, Martinović T, Kravić-Stevović T, Ćirić D, Marković ZJ, Isaković A, Trajković V. Graphene Quantum Dots show protective effect in animal model of neuroinflammation. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade. 2023;:114.
https://hdl.handle.net/21.15107/rcub_vinar_11057 .

Tasić, Jelena, Vidičević Novaković, Sašenka, Stanojević, Željka, Paunović, Verica, Petričević, Saša, Martinović, Tamara, Kravić-Stevović, Tamara, Ćirić, Darko, Marković, Zoran J., Isaković, Aleksandra, Trajković, Vladimir, "Graphene Quantum Dots show protective effect in animal model of neuroinflammation" in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade (2023):114,
https://hdl.handle.net/21.15107/rcub_vinar_11057 .

TY  - JOUR
AU  - Tošić, Jelena
AU  - Stanojević, Željka
AU  - Vidičević, Sašenka
AU  - Isaković, Aleksandra J.
AU  - Ćirić, Darko
AU  - Martinović, Tamara
AU  - Kravić-Stevović, Tamara K.
AU  - Bumbaširević, Vladimir Ž.
AU  - Paunović, Verica G.
AU  - Jovanović, Svetlana P.
AU  - Todorović-Marković, Biljana
AU  - Marković, Zoran M.
AU  - Danko, Martin
AU  - Mičušik, Matej
AU  - Spitalsky, Zdenko
AU  - Trajković, Vladimir S.
PY  - 2019
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0028390818308621
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8015
AB  - We investigated the therapeutic capacity of nano-sized graphene sheets, called graphene quantum dots (GQD), in experimental autoimmune encephalomyelitis (EAE), an animal model of immune-mediated central nervous system (CNS) damage. Intraperitoneally administered GQD (10 mg/kg/day) accumulated in the lymph node and CNS cells of Dark Agouti rats in which EAE was induced by immunization with spinal cord homogenate in complete Freund's adjuvant. GQD significantly reduced clinical signs of EAE when applied throughout the course of the disease (day 0–32), while the protection was less pronounced if the treatment was limited to the induction (day 0–7 post-immunization) or effector (from day 8 onwards) phase of the disease. GQD treatment diminished immune infiltration, demyelination, axonal damage, and apoptotic death in the CNS of EAE animals. GQD also reduced the numbers of interferon-γ-expressing T helper (Th)1 cells, as well as the expression of Th1 transcription factor T-bet and proinflammatory cytokines tumor necrosis factor, interleukin-1, and granulocyte-macrophage colony-stimulating factor in the lymph nodes and CNS immune infitrates. The protective effect of GQD in EAE was associated with the activation of p38 and p42/44 mitogen-activated protein kinases (MAPK) and Akt in the lymph nodes and/or CNS. Finally, GQD protected oligodendrocytes and neurons from T cell-mediated damage in the in vitro conditions. Collectively, these data demonstrate the ability of GQD to gain access to both immune and CNS cells during neuroinflammation, and to alleviate immune-mediated CNS damage by modulating MAPK/Akt signaling and encephalitogenic Th1 immune response. © 2018 Elsevier Ltd
T2  - Neuropharmacology
T1  - Graphene quantum dots inhibit T cell-mediated neuroinflammation in rats
VL  - 146
SP  - 95
EP  - 108
DO  - 10.1016/j.neuropharm.2018.11.030
ER  - 

@article{
author = "Tošić, Jelena and Stanojević, Željka and Vidičević, Sašenka and Isaković, Aleksandra J. and Ćirić, Darko and Martinović, Tamara and Kravić-Stevović, Tamara K. and Bumbaširević, Vladimir Ž. and Paunović, Verica G. and Jovanović, Svetlana P. and Todorović-Marković, Biljana and Marković, Zoran M. and Danko, Martin and Mičušik, Matej and Spitalsky, Zdenko and Trajković, Vladimir S.",
year = "2019",
abstract = "We investigated the therapeutic capacity of nano-sized graphene sheets, called graphene quantum dots (GQD), in experimental autoimmune encephalomyelitis (EAE), an animal model of immune-mediated central nervous system (CNS) damage. Intraperitoneally administered GQD (10 mg/kg/day) accumulated in the lymph node and CNS cells of Dark Agouti rats in which EAE was induced by immunization with spinal cord homogenate in complete Freund's adjuvant. GQD significantly reduced clinical signs of EAE when applied throughout the course of the disease (day 0–32), while the protection was less pronounced if the treatment was limited to the induction (day 0–7 post-immunization) or effector (from day 8 onwards) phase of the disease. GQD treatment diminished immune infiltration, demyelination, axonal damage, and apoptotic death in the CNS of EAE animals. GQD also reduced the numbers of interferon-γ-expressing T helper (Th)1 cells, as well as the expression of Th1 transcription factor T-bet and proinflammatory cytokines tumor necrosis factor, interleukin-1, and granulocyte-macrophage colony-stimulating factor in the lymph nodes and CNS immune infitrates. The protective effect of GQD in EAE was associated with the activation of p38 and p42/44 mitogen-activated protein kinases (MAPK) and Akt in the lymph nodes and/or CNS. Finally, GQD protected oligodendrocytes and neurons from T cell-mediated damage in the in vitro conditions. Collectively, these data demonstrate the ability of GQD to gain access to both immune and CNS cells during neuroinflammation, and to alleviate immune-mediated CNS damage by modulating MAPK/Akt signaling and encephalitogenic Th1 immune response. © 2018 Elsevier Ltd",
journal = "Neuropharmacology",
title = "Graphene quantum dots inhibit T cell-mediated neuroinflammation in rats",
volume = "146",
pages = "95-108",
doi = "10.1016/j.neuropharm.2018.11.030"
}

Tošić, J., Stanojević, Ž., Vidičević, S., Isaković, A. J., Ćirić, D., Martinović, T., Kravić-Stevović, T. K., Bumbaširević, V. Ž., Paunović, V. G., Jovanović, S. P., Todorović-Marković, B., Marković, Z. M., Danko, M., Mičušik, M., Spitalsky, Z.,& Trajković, V. S.. (2019). Graphene quantum dots inhibit T cell-mediated neuroinflammation in rats. in Neuropharmacology, 146, 95-108.
https://doi.org/10.1016/j.neuropharm.2018.11.030

Tošić J, Stanojević Ž, Vidičević S, Isaković AJ, Ćirić D, Martinović T, Kravić-Stevović TK, Bumbaširević VŽ, Paunović VG, Jovanović SP, Todorović-Marković B, Marković ZM, Danko M, Mičušik M, Spitalsky Z, Trajković VS. Graphene quantum dots inhibit T cell-mediated neuroinflammation in rats. in Neuropharmacology. 2019;146:95-108.
doi:10.1016/j.neuropharm.2018.11.030 .

Tošić, Jelena, Stanojević, Željka, Vidičević, Sašenka, Isaković, Aleksandra J., Ćirić, Darko, Martinović, Tamara, Kravić-Stevović, Tamara K., Bumbaširević, Vladimir Ž., Paunović, Verica G., Jovanović, Svetlana P., Todorović-Marković, Biljana, Marković, Zoran M., Danko, Martin, Mičušik, Matej, Spitalsky, Zdenko, Trajković, Vladimir S., "Graphene quantum dots inhibit T cell-mediated neuroinflammation in rats" in Neuropharmacology, 146 (2019):95-108,
https://doi.org/10.1016/j.neuropharm.2018.11.030 . .

TY  - CONF
AU  - Tošić, Jelena
AU  - Vidičević, Sašenka
AU  - Stanojević, Željka
AU  - Paunović, Verica G.
AU  - Petricevic, S.
AU  - Martinović, Tamara
AU  - Kravić-Stevović, Tamara K.
AU  - Ćirić, Darko
AU  - Marković, Zoran M.
AU  - Isaković, Aleksandra J.
AU  - Trajković, Vladimir S.
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7160
C3  - European Neuropsychopharmacology
T1  - Graphene quantum dots show protective effect on a model of experimental autoimmune encephalomyelitis
VL  - 26
SP  - S211
EP  - S212
DO  - 10.1016/S0924-977X(16)31060-4
ER  - 

@conference{
author = "Tošić, Jelena and Vidičević, Sašenka and Stanojević, Željka and Paunović, Verica G. and Petricevic, S. and Martinović, Tamara and Kravić-Stevović, Tamara K. and Ćirić, Darko and Marković, Zoran M. and Isaković, Aleksandra J. and Trajković, Vladimir S.",
year = "2016",
journal = "European Neuropsychopharmacology",
title = "Graphene quantum dots show protective effect on a model of experimental autoimmune encephalomyelitis",
volume = "26",
pages = "S211-S212",
doi = "10.1016/S0924-977X(16)31060-4"
}

Tošić, J., Vidičević, S., Stanojević, Ž., Paunović, V. G., Petricevic, S., Martinović, T., Kravić-Stevović, T. K., Ćirić, D., Marković, Z. M., Isaković, A. J.,& Trajković, V. S.. (2016). Graphene quantum dots show protective effect on a model of experimental autoimmune encephalomyelitis. in European Neuropsychopharmacology, 26, S211-S212.
https://doi.org/10.1016/S0924-977X(16)31060-4

Tošić J, Vidičević S, Stanojević Ž, Paunović VG, Petricevic S, Martinović T, Kravić-Stevović TK, Ćirić D, Marković ZM, Isaković AJ, Trajković VS. Graphene quantum dots show protective effect on a model of experimental autoimmune encephalomyelitis. in European Neuropsychopharmacology. 2016;26:S211-S212.
doi:10.1016/S0924-977X(16)31060-4 .

Tošić, Jelena, Vidičević, Sašenka, Stanojević, Željka, Paunović, Verica G., Petricevic, S., Martinović, Tamara, Kravić-Stevović, Tamara K., Ćirić, Darko, Marković, Zoran M., Isaković, Aleksandra J., Trajković, Vladimir S., "Graphene quantum dots show protective effect on a model of experimental autoimmune encephalomyelitis" in European Neuropsychopharmacology, 26 (2016):S211-S212,
https://doi.org/10.1016/S0924-977X(16)31060-4 . .

TY  - CONF
AU  - Seke, Mariana
AU  - Popadić, Dušan
AU  - Isaković, Aleksandra
AU  - Marković, Ivanka
PY  - 2008
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12773
AB  - Mnoge ćelije u CNS-u preuzimaju nukleozide iz vanćelijske teĉnosti i koriste ih za sintezu nukleotida u putevima uštede. Nukleozidi se kroz membranu astrocita transportuje putem dve genske familije nukleozidnih transportera: ekvilibrativnih (ENT1 i ENT2) koji omogućavaju jednosmernu olakšanu difuziju i koncentrativnih (CNT2) koji omogućavaju jednosmerni sekundarno aktivni transport kroz ćelijsku membranu. Cilj ovog istraţivanja je bio ispitivanje ekspresije razliĉitih klasa nukleozidnih transportera na primarno kultivisanim astrocitima pacova, kao i uticaj hroniĉno povećane koncentracije adenozina u vanćelijskom medijumu na stepen njihove ekspresije. Eksperimenti su raĊeni u primarnoj kulturi astrocita pacova soja Wistar. Ćelije su u toku 21 dana kontinuirano tretirane adenozinom u koncentracijama od 25µM i 100µM. Kvantifikacija genske ekspresije je vršena RT-qPCR analizom na svakih 7 dana i izraţena je kao ΔCt vrednost u odmosu na vrednost koamplifikovanog β-aktina. Rezultati su pokazali da se u primarnim astrocitima pacova eksprimiraju transporteri i ekvilibrativnog i koncentrativnog tipa. Najveću ekspresiju nakon 7-og dana u kulturi je pokazao koncentrativni transporter CNT 2 (ΔCt=7,13±0,42), dok je stepen ekspresije za ekvilibrativne transportere bio nešto niţi za ENT 1 ΔCt=9,48±0,29, a za ENT 2 ΔCt=8,67±0,24. TakoĊe je uoĉeno da se tokom kultivisanja u vremenskom periodu od 21-og dana postepeno smanjuje genska ekspresija svih ispitivanih transportera: za CNT 2 ΔCt=12,75±0,51; za ENT 1 ΔCt=12,78±0,41; i za ENT 2 ΔCt=12,37±0,44. U uslovima kontinuiranog prisustva adenozina u primarnoj kulturi astrocita (25µM, odnosno 100µM) nakon 7,14 i 21 dana, nije došlo do znaĉajne promene u ekpresiji ni jednog od ispitivanih transportera u odnosnu na populaciju ćelija koja nije bila izloţena tretmanu adenozinom.
C3  - VII/XIII Kongres neurologa Srbije sa međunarodnim uĉešćem : IV Kongres društva za neuronauke Srbije sa međunarodnim uĉešćem : I Simpozijum neuroloških medicinskih sestara - Tehniĉara Srbije : Zbornik sažetaka
T1  - Ekspresija nukleozidnih transportera u primarnoj kulturi astrocita pacova
SP  - 381
EP  - 382
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12773
ER  - 

@conference{
author = "Seke, Mariana and Popadić, Dušan and Isaković, Aleksandra and Marković, Ivanka",
year = "2008",
abstract = "Mnoge ćelije u CNS-u preuzimaju nukleozide iz vanćelijske teĉnosti i koriste ih za sintezu nukleotida u putevima uštede. Nukleozidi se kroz membranu astrocita transportuje putem dve genske familije nukleozidnih transportera: ekvilibrativnih (ENT1 i ENT2) koji omogućavaju jednosmernu olakšanu difuziju i koncentrativnih (CNT2) koji omogućavaju jednosmerni sekundarno aktivni transport kroz ćelijsku membranu. Cilj ovog istraţivanja je bio ispitivanje ekspresije razliĉitih klasa nukleozidnih transportera na primarno kultivisanim astrocitima pacova, kao i uticaj hroniĉno povećane koncentracije adenozina u vanćelijskom medijumu na stepen njihove ekspresije. Eksperimenti su raĊeni u primarnoj kulturi astrocita pacova soja Wistar. Ćelije su u toku 21 dana kontinuirano tretirane adenozinom u koncentracijama od 25µM i 100µM. Kvantifikacija genske ekspresije je vršena RT-qPCR analizom na svakih 7 dana i izraţena je kao ΔCt vrednost u odmosu na vrednost koamplifikovanog β-aktina. Rezultati su pokazali da se u primarnim astrocitima pacova eksprimiraju transporteri i ekvilibrativnog i koncentrativnog tipa. Najveću ekspresiju nakon 7-og dana u kulturi je pokazao koncentrativni transporter CNT 2 (ΔCt=7,13±0,42), dok je stepen ekspresije za ekvilibrativne transportere bio nešto niţi za ENT 1 ΔCt=9,48±0,29, a za ENT 2 ΔCt=8,67±0,24. TakoĊe je uoĉeno da se tokom kultivisanja u vremenskom periodu od 21-og dana postepeno smanjuje genska ekspresija svih ispitivanih transportera: za CNT 2 ΔCt=12,75±0,51; za ENT 1 ΔCt=12,78±0,41; i za ENT 2 ΔCt=12,37±0,44. U uslovima kontinuiranog prisustva adenozina u primarnoj kulturi astrocita (25µM, odnosno 100µM) nakon 7,14 i 21 dana, nije došlo do znaĉajne promene u ekpresiji ni jednog od ispitivanih transportera u odnosnu na populaciju ćelija koja nije bila izloţena tretmanu adenozinom.",
journal = "VII/XIII Kongres neurologa Srbije sa međunarodnim uĉešćem : IV Kongres društva za neuronauke Srbije sa međunarodnim uĉešćem : I Simpozijum neuroloških medicinskih sestara - Tehniĉara Srbije : Zbornik sažetaka",
title = "Ekspresija nukleozidnih transportera u primarnoj kulturi astrocita pacova",
pages = "381-382",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12773"
}

Seke, M., Popadić, D., Isaković, A.,& Marković, I.. (2008). Ekspresija nukleozidnih transportera u primarnoj kulturi astrocita pacova. in VII/XIII Kongres neurologa Srbije sa međunarodnim uĉešćem : IV Kongres društva za neuronauke Srbije sa međunarodnim uĉešćem : I Simpozijum neuroloških medicinskih sestara - Tehniĉara Srbije : Zbornik sažetaka, 381-382.
https://hdl.handle.net/21.15107/rcub_vinar_12773

Seke M, Popadić D, Isaković A, Marković I. Ekspresija nukleozidnih transportera u primarnoj kulturi astrocita pacova. in VII/XIII Kongres neurologa Srbije sa međunarodnim uĉešćem : IV Kongres društva za neuronauke Srbije sa međunarodnim uĉešćem : I Simpozijum neuroloških medicinskih sestara - Tehniĉara Srbije : Zbornik sažetaka. 2008;:381-382.
https://hdl.handle.net/21.15107/rcub_vinar_12773 .

Seke, Mariana, Popadić, Dušan, Isaković, Aleksandra, Marković, Ivanka, "Ekspresija nukleozidnih transportera u primarnoj kulturi astrocita pacova" in VII/XIII Kongres neurologa Srbije sa međunarodnim uĉešćem : IV Kongres društva za neuronauke Srbije sa međunarodnim uĉešćem : I Simpozijum neuroloških medicinskih sestara - Tehniĉara Srbije : Zbornik sažetaka (2008):381-382,
https://hdl.handle.net/21.15107/rcub_vinar_12773 .

TY  - JOUR
AU  - Harhaji, Ljubica M.
AU  - Isaković, Aleksandra J.
AU  - Vucicevic, Ljubica
AU  - Janjetović, Kristina D.
AU  - Misirkić, Maja
AU  - Marković, Zoran M.
AU  - Todorović-Marković, Biljana
AU  - Nikolić, Nadežda S.
AU  - Vranješ-Đurić, Sanja
AU  - Nikolić, Zoran M.
AU  - Trajković, Vladimir S.
PY  - 2008
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3445
AB  - Purpose. The fullerene (C-60/C-70 mixture-C-60/70) nanocrystalline suspension prepared by solvent exchange method using tetrahydrofyran (THF/nC(60/70)) and polyhydroxylated C-60/70 [C-60/70(OH)(n)] were compared for their ability to modulate cytotoxicity of the proinflammatory cytokine tumor necrosis factor (TNT). Materials and Methods. TNF-induced cytotoxicity was assessed in L929 fibrosarcoma cells by crystal violet assay. The type of cell death (apoptosis/necrosis), production of reactive oxygen species, mitochondrial depolarization and caspase activation were determined by flow cytometry using the appropriate reporter dyes. Results. THF/nC(60/70) augmented, while C-60/70(OH)(n) reduced the cytotoxicity of TNF. The numbers of cells undergoing apoptosis/necrosis, as well as of those displaying the activation of apoptosis-inducing enzymes of caspase family, were respectively increased or reduced by THF/nC(60/70) or C-60/70(OH)(n). The antioxidant N-acetylcysteine and mitochondrial permeability transition inhibitor cyclosporin A each partly blocked the cytotoxic action of TNF, indicating the involvement of oxidative stress and mitochondrial dysfunction in the TNF cytotoxicity. Accordingly, THF/nC(60/70) or C-60/70(OH)(n) potentiated or suppressed, respectively, TNF-triggered oxidative stress and mitochondrial depolarization. Conclusion. The ability of different fullerene preparations to modulate TNF-induced oxidative stress and subsequent cell death suggests their potential value in the TNF-based cancer therapy or prevention of TNF-dependent tissue damage.
T2  - Pharmaceutical Research
T1  - Modulation of tumor necrosis factor-mediated cell death by fullerenes
VL  - 25
IS  - 6
SP  - 1365
EP  - 1376
DO  - 10.1007/s11095-007-9486-y
ER  - 

@article{
author = "Harhaji, Ljubica M. and Isaković, Aleksandra J. and Vucicevic, Ljubica and Janjetović, Kristina D. and Misirkić, Maja and Marković, Zoran M. and Todorović-Marković, Biljana and Nikolić, Nadežda S. and Vranješ-Đurić, Sanja and Nikolić, Zoran M. and Trajković, Vladimir S.",
year = "2008",
abstract = "Purpose. The fullerene (C-60/C-70 mixture-C-60/70) nanocrystalline suspension prepared by solvent exchange method using tetrahydrofyran (THF/nC(60/70)) and polyhydroxylated C-60/70 [C-60/70(OH)(n)] were compared for their ability to modulate cytotoxicity of the proinflammatory cytokine tumor necrosis factor (TNT). Materials and Methods. TNF-induced cytotoxicity was assessed in L929 fibrosarcoma cells by crystal violet assay. The type of cell death (apoptosis/necrosis), production of reactive oxygen species, mitochondrial depolarization and caspase activation were determined by flow cytometry using the appropriate reporter dyes. Results. THF/nC(60/70) augmented, while C-60/70(OH)(n) reduced the cytotoxicity of TNF. The numbers of cells undergoing apoptosis/necrosis, as well as of those displaying the activation of apoptosis-inducing enzymes of caspase family, were respectively increased or reduced by THF/nC(60/70) or C-60/70(OH)(n). The antioxidant N-acetylcysteine and mitochondrial permeability transition inhibitor cyclosporin A each partly blocked the cytotoxic action of TNF, indicating the involvement of oxidative stress and mitochondrial dysfunction in the TNF cytotoxicity. Accordingly, THF/nC(60/70) or C-60/70(OH)(n) potentiated or suppressed, respectively, TNF-triggered oxidative stress and mitochondrial depolarization. Conclusion. The ability of different fullerene preparations to modulate TNF-induced oxidative stress and subsequent cell death suggests their potential value in the TNF-based cancer therapy or prevention of TNF-dependent tissue damage.",
journal = "Pharmaceutical Research",
title = "Modulation of tumor necrosis factor-mediated cell death by fullerenes",
volume = "25",
number = "6",
pages = "1365-1376",
doi = "10.1007/s11095-007-9486-y"
}

Harhaji, L. M., Isaković, A. J., Vucicevic, L., Janjetović, K. D., Misirkić, M., Marković, Z. M., Todorović-Marković, B., Nikolić, N. S., Vranješ-Đurić, S., Nikolić, Z. M.,& Trajković, V. S.. (2008). Modulation of tumor necrosis factor-mediated cell death by fullerenes. in Pharmaceutical Research, 25(6), 1365-1376.
https://doi.org/10.1007/s11095-007-9486-y

Harhaji LM, Isaković AJ, Vucicevic L, Janjetović KD, Misirkić M, Marković ZM, Todorović-Marković B, Nikolić NS, Vranješ-Đurić S, Nikolić ZM, Trajković VS. Modulation of tumor necrosis factor-mediated cell death by fullerenes. in Pharmaceutical Research. 2008;25(6):1365-1376.
doi:10.1007/s11095-007-9486-y .

Harhaji, Ljubica M., Isaković, Aleksandra J., Vucicevic, Ljubica, Janjetović, Kristina D., Misirkić, Maja, Marković, Zoran M., Todorović-Marković, Biljana, Nikolić, Nadežda S., Vranješ-Đurić, Sanja, Nikolić, Zoran M., Trajković, Vladimir S., "Modulation of tumor necrosis factor-mediated cell death by fullerenes" in Pharmaceutical Research, 25, no. 6 (2008):1365-1376,
https://doi.org/10.1007/s11095-007-9486-y . .

TY  - JOUR
AU  - Marković, Zoran M.
AU  - Todorović-Marković, Biljana
AU  - Kleut, Duška
AU  - Nikolić, Nadežda S.
AU  - Vranješ-Đurić, Sanja
AU  - Misirkić, Maja
AU  - Vucicevic, Ljubica
AU  - Janjetović, Kristina D.
AU  - Isaković, Aleksandra J.
AU  - Harhaji, Ljubica M.
AU  - Babić-Stojić, Branka S.
AU  - Dramićanin, Miroslav
AU  - Trajković, Vladimir S.
PY  - 2007
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3322
AB  - Because of the ability to induce cell death in certain conditions, the fullerenes (C-60) are potential anticancer and toxic agents. The colloidal suspension of crystalline C-60 (nano-C-60, nC(60)) is extremely toxic, but the mechanisms of its cytotoxicity are not completely understood. By combining experimental analysis and mathematical modelling, we investigate the requirements for the reactive oxygen species (ROS)-mediated cytotoxicity of different nC(60) suspensions, prepared by solvent exchange method in tetrahydrofuran (THF/nC(60)) and ethanol (EtOH/nC(60)), or by extended mixing in water (aqu/nC(60)). With regard to their capacity to generate ROS and cause mitochondrial depolarization followed by necrotic cell death, the nC(60) suspensions are ranked in the following order: THF/nC(60) GT EtOH/nC(60) GT aqu/nC(60). Mathematical modelling of singlet oxygen (O-1(2)) generation indicates that the O-1(2)-quenching power (THF/nC(60) LT EtOH/nC(60) LT aqU/nC(60)) of the solvent intercalated in the fullerene crystals determines their ability to produce ROS and cause cell damage. These data could. have important implications for toxicology and biomedical application of colloidal fullerenes. (C) 2007 Elsevier Ltd. All rights reserved.
T2  - Biomaterials
T1  - The mechanism of cell-damaging reactive oxygen generation by colloidal fullerenes
VL  - 28
IS  - 36
SP  - 5437
EP  - 5448
DO  - 10.1016/j.biomaterials.2007.09.002
ER  - 

@article{
author = "Marković, Zoran M. and Todorović-Marković, Biljana and Kleut, Duška and Nikolić, Nadežda S. and Vranješ-Đurić, Sanja and Misirkić, Maja and Vucicevic, Ljubica and Janjetović, Kristina D. and Isaković, Aleksandra J. and Harhaji, Ljubica M. and Babić-Stojić, Branka S. and Dramićanin, Miroslav and Trajković, Vladimir S.",
year = "2007",
abstract = "Because of the ability to induce cell death in certain conditions, the fullerenes (C-60) are potential anticancer and toxic agents. The colloidal suspension of crystalline C-60 (nano-C-60, nC(60)) is extremely toxic, but the mechanisms of its cytotoxicity are not completely understood. By combining experimental analysis and mathematical modelling, we investigate the requirements for the reactive oxygen species (ROS)-mediated cytotoxicity of different nC(60) suspensions, prepared by solvent exchange method in tetrahydrofuran (THF/nC(60)) and ethanol (EtOH/nC(60)), or by extended mixing in water (aqu/nC(60)). With regard to their capacity to generate ROS and cause mitochondrial depolarization followed by necrotic cell death, the nC(60) suspensions are ranked in the following order: THF/nC(60) GT EtOH/nC(60) GT aqu/nC(60). Mathematical modelling of singlet oxygen (O-1(2)) generation indicates that the O-1(2)-quenching power (THF/nC(60) LT EtOH/nC(60) LT aqU/nC(60)) of the solvent intercalated in the fullerene crystals determines their ability to produce ROS and cause cell damage. These data could. have important implications for toxicology and biomedical application of colloidal fullerenes. (C) 2007 Elsevier Ltd. All rights reserved.",
journal = "Biomaterials",
title = "The mechanism of cell-damaging reactive oxygen generation by colloidal fullerenes",
volume = "28",
number = "36",
pages = "5437-5448",
doi = "10.1016/j.biomaterials.2007.09.002"
}

Marković, Z. M., Todorović-Marković, B., Kleut, D., Nikolić, N. S., Vranješ-Đurić, S., Misirkić, M., Vucicevic, L., Janjetović, K. D., Isaković, A. J., Harhaji, L. M., Babić-Stojić, B. S., Dramićanin, M.,& Trajković, V. S.. (2007). The mechanism of cell-damaging reactive oxygen generation by colloidal fullerenes. in Biomaterials, 28(36), 5437-5448.
https://doi.org/10.1016/j.biomaterials.2007.09.002

Marković ZM, Todorović-Marković B, Kleut D, Nikolić NS, Vranješ-Đurić S, Misirkić M, Vucicevic L, Janjetović KD, Isaković AJ, Harhaji LM, Babić-Stojić BS, Dramićanin M, Trajković VS. The mechanism of cell-damaging reactive oxygen generation by colloidal fullerenes. in Biomaterials. 2007;28(36):5437-5448.
doi:10.1016/j.biomaterials.2007.09.002 .

Marković, Zoran M., Todorović-Marković, Biljana, Kleut, Duška, Nikolić, Nadežda S., Vranješ-Đurić, Sanja, Misirkić, Maja, Vucicevic, Ljubica, Janjetović, Kristina D., Isaković, Aleksandra J., Harhaji, Ljubica M., Babić-Stojić, Branka S., Dramićanin, Miroslav, Trajković, Vladimir S., "The mechanism of cell-damaging reactive oxygen generation by colloidal fullerenes" in Biomaterials, 28, no. 36 (2007):5437-5448,
https://doi.org/10.1016/j.biomaterials.2007.09.002 . .

TY  - JOUR
AU  - Harhaji, Ljubica M.
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Popadic, Dusan
AU  - Isaković, Aleksandra J.
AU  - Todorović-Marković, Biljana
AU  - Trajković, Vladimir S.
PY  - 2007
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3225
AB  - We demonstrate the capacity of an herbal anthraquinone aloe emodin to reduce the cytotoxicity of the proinflammatory cytokine tumor necrosis factor (TNF) towards L929 mouse fibrosarcoma and U251 human glioma cell lines. Aloe emodin inhibited both TNF-induced cell necrosis and apoptosis, but it did not reduce cell death induced by UV radiation or hydrogen peroxide. Aloe emodin inhibited both basal and TNF-triggered activation of extracellular signal-regulated kinase (ERK), and a selective blockade of ERK activation mimicked the cytoprotective action of the drug. On the other hand, aloe emodin did not affect TNF-induced activation of p38 mitogen-activated protein kinase or generation of reactive oxygen species. The combination of aloe emodin and TNF caused an intracellular appearance of acidified autophagic vesicles, and the inhibition of autophagy with bafilomycin or 3-methyladenine efficiently blocked the cytoprotective action of aloe emodin. These data indicate that aloe emodin could prevent TNF-triggered cell death through mechanisms involving induction of autophagy and blockade of ERK activation. (C) 2007 Elsevier B.V. All rights reserved.
T2  - European Journal of Pharmacology
T1  - Aloe emodin inhibits the cytotoxic action of tumor necrosis factor
VL  - 568
IS  - 1-3
SP  - 248
EP  - 259
DO  - 10.1016/j.ejphar.2007.04.029
ER  - 

@article{
author = "Harhaji, Ljubica M. and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Popadic, Dusan and Isaković, Aleksandra J. and Todorović-Marković, Biljana and Trajković, Vladimir S.",
year = "2007",
abstract = "We demonstrate the capacity of an herbal anthraquinone aloe emodin to reduce the cytotoxicity of the proinflammatory cytokine tumor necrosis factor (TNF) towards L929 mouse fibrosarcoma and U251 human glioma cell lines. Aloe emodin inhibited both TNF-induced cell necrosis and apoptosis, but it did not reduce cell death induced by UV radiation or hydrogen peroxide. Aloe emodin inhibited both basal and TNF-triggered activation of extracellular signal-regulated kinase (ERK), and a selective blockade of ERK activation mimicked the cytoprotective action of the drug. On the other hand, aloe emodin did not affect TNF-induced activation of p38 mitogen-activated protein kinase or generation of reactive oxygen species. The combination of aloe emodin and TNF caused an intracellular appearance of acidified autophagic vesicles, and the inhibition of autophagy with bafilomycin or 3-methyladenine efficiently blocked the cytoprotective action of aloe emodin. These data indicate that aloe emodin could prevent TNF-triggered cell death through mechanisms involving induction of autophagy and blockade of ERK activation. (C) 2007 Elsevier B.V. All rights reserved.",
journal = "European Journal of Pharmacology",
title = "Aloe emodin inhibits the cytotoxic action of tumor necrosis factor",
volume = "568",
number = "1-3",
pages = "248-259",
doi = "10.1016/j.ejphar.2007.04.029"
}

Harhaji, L. M., Mijatović, S., Maksimović-Ivanić, D., Popadic, D., Isaković, A. J., Todorović-Marković, B.,& Trajković, V. S.. (2007). Aloe emodin inhibits the cytotoxic action of tumor necrosis factor. in European Journal of Pharmacology, 568(1-3), 248-259.
https://doi.org/10.1016/j.ejphar.2007.04.029

Harhaji LM, Mijatović S, Maksimović-Ivanić D, Popadic D, Isaković AJ, Todorović-Marković B, Trajković VS. Aloe emodin inhibits the cytotoxic action of tumor necrosis factor. in European Journal of Pharmacology. 2007;568(1-3):248-259.
doi:10.1016/j.ejphar.2007.04.029 .

Harhaji, Ljubica M., Mijatović, Sanja, Maksimović-Ivanić, Danijela, Popadic, Dusan, Isaković, Aleksandra J., Todorović-Marković, Biljana, Trajković, Vladimir S., "Aloe emodin inhibits the cytotoxic action of tumor necrosis factor" in European Journal of Pharmacology, 568, no. 1-3 (2007):248-259,
https://doi.org/10.1016/j.ejphar.2007.04.029 . .

TY  - JOUR
AU  - Isaković, Aleksandra J.
AU  - Harhaji, Ljubica M.
AU  - Stevanović, D.
AU  - Marković, Zoran M.
AU  - Sumarac-Dumanovic, M.
AU  - Starčević, Vesna
AU  - Micic, D.
AU  - Trajković, Vladimir S.
PY  - 2007
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3198
AB  - The present study reports for the first time a dual antiglioma effect of the well-known antidiabetic drug metformin. In low-density cultures of the C6 rat glioma cell line, metformin blocked the cell cycle progression in G(0)/G(1) phase without inducing significant cell death. In confluent C6 cultures, on the other hand, metformin caused massive induction of caspase-dependent apoptosis associated with c-Jun N-terminal kinase (JNK) activation, mitochondrial depolarization and oxidative stress. Metformin-triggered apoptosis was completely prevented by agents that block mitochondrial permeability transition (cyclosporin A) and oxygen radical production (N-acetylcisteine), while the inhibitors of JNK activation (SP600125) or glycolysis (sodium fluoride, iodoacetate) provided partial protection. The antiglioma effect of metformin was reduced by compound C, an inhibitor of AMP-activated protein kinase (AMPK), and was mimicked by the AMPK agonist AICAR. Similar effects were observed in the human glioma cell line U251, while rat primary astrocytes were completely resistant to the antiproliferative and proapoptotic action of metformin.
T2  - Cellular and Molecular Life Sciences / CMLS
T1  - Dual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent apoptosis
VL  - 64
IS  - 10
SP  - 1290
EP  - 1302
DO  - 10.1007/s00018-007-7080-4
ER  - 

@article{
author = "Isaković, Aleksandra J. and Harhaji, Ljubica M. and Stevanović, D. and Marković, Zoran M. and Sumarac-Dumanovic, M. and Starčević, Vesna and Micic, D. and Trajković, Vladimir S.",
year = "2007",
abstract = "The present study reports for the first time a dual antiglioma effect of the well-known antidiabetic drug metformin. In low-density cultures of the C6 rat glioma cell line, metformin blocked the cell cycle progression in G(0)/G(1) phase without inducing significant cell death. In confluent C6 cultures, on the other hand, metformin caused massive induction of caspase-dependent apoptosis associated with c-Jun N-terminal kinase (JNK) activation, mitochondrial depolarization and oxidative stress. Metformin-triggered apoptosis was completely prevented by agents that block mitochondrial permeability transition (cyclosporin A) and oxygen radical production (N-acetylcisteine), while the inhibitors of JNK activation (SP600125) or glycolysis (sodium fluoride, iodoacetate) provided partial protection. The antiglioma effect of metformin was reduced by compound C, an inhibitor of AMP-activated protein kinase (AMPK), and was mimicked by the AMPK agonist AICAR. Similar effects were observed in the human glioma cell line U251, while rat primary astrocytes were completely resistant to the antiproliferative and proapoptotic action of metformin.",
journal = "Cellular and Molecular Life Sciences / CMLS",
title = "Dual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent apoptosis",
volume = "64",
number = "10",
pages = "1290-1302",
doi = "10.1007/s00018-007-7080-4"
}

Isaković, A. J., Harhaji, L. M., Stevanović, D., Marković, Z. M., Sumarac-Dumanovic, M., Starčević, V., Micic, D.,& Trajković, V. S.. (2007). Dual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent apoptosis. in Cellular and Molecular Life Sciences / CMLS, 64(10), 1290-1302.
https://doi.org/10.1007/s00018-007-7080-4

Isaković AJ, Harhaji LM, Stevanović D, Marković ZM, Sumarac-Dumanovic M, Starčević V, Micic D, Trajković VS. Dual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent apoptosis. in Cellular and Molecular Life Sciences / CMLS. 2007;64(10):1290-1302.
doi:10.1007/s00018-007-7080-4 .

Isaković, Aleksandra J., Harhaji, Ljubica M., Stevanović, D., Marković, Zoran M., Sumarac-Dumanovic, M., Starčević, Vesna, Micic, D., Trajković, Vladimir S., "Dual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent apoptosis" in Cellular and Molecular Life Sciences / CMLS, 64, no. 10 (2007):1290-1302,
https://doi.org/10.1007/s00018-007-7080-4 . .

TY  - JOUR
AU  - Isaković, Aleksandra J.
AU  - Marković, Zoran M.
AU  - Nikolić, Nadežda S.
AU  - Todorović-Marković, Biljana
AU  - Vranješ-Đurić, Sanja
AU  - Harhaji, Ljubica M.
AU  - Raičević, Nevena
AU  - Romčević, Nebojša Ž.
AU  - Vasiljević-Radović, Dana
AU  - Dramićanin, Miroslav
AU  - Trajković, Vladimir S.
PY  - 2006
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3076
AB  - We investigated the effect of gamma-irradiation on the cytotoxicity of pure C-60 solubilized in water by using tetrahydrofuran (THF/n-C-60 or THF/n-C-60). In contrast to THF/n-C-60, its gamma-irradiated counterpart failed to generate oxygen radicals and cause extracellular signal-regulated kinase (ERK)-dependent necrotic cell death in various types of mammalian cells. Moreover, gamma-irradiated THF/n-C-60 protected cells from the oxidative stress induced by native THF/n-C-60 or hydrogen peroxide. The observed biological effects were associated with of THF and subsequent derivatization of the n-C-60 surface. These results for the first time demonstrate gamma-irradiation-mediated changes in the physico-chemical properties of THF-prepared nanocrystalline C-60, resulting in a complete loss of its cytotoxic effect and its conversion to a cytoprotective agent. (c) 2006 Elsevier Ltd. All rights reserved.
T2  - Biomaterials
T1  - Inactivation of nanocrystalline C-60 cytotoxicity by gamma-irradiation
VL  - 27
IS  - 29
SP  - 5049
EP  - 5058
DO  - 10.1016/j.biomaterials.2006.05.047
ER  - 

@article{
author = "Isaković, Aleksandra J. and Marković, Zoran M. and Nikolić, Nadežda S. and Todorović-Marković, Biljana and Vranješ-Đurić, Sanja and Harhaji, Ljubica M. and Raičević, Nevena and Romčević, Nebojša Ž. and Vasiljević-Radović, Dana and Dramićanin, Miroslav and Trajković, Vladimir S.",
year = "2006",
abstract = "We investigated the effect of gamma-irradiation on the cytotoxicity of pure C-60 solubilized in water by using tetrahydrofuran (THF/n-C-60 or THF/n-C-60). In contrast to THF/n-C-60, its gamma-irradiated counterpart failed to generate oxygen radicals and cause extracellular signal-regulated kinase (ERK)-dependent necrotic cell death in various types of mammalian cells. Moreover, gamma-irradiated THF/n-C-60 protected cells from the oxidative stress induced by native THF/n-C-60 or hydrogen peroxide. The observed biological effects were associated with of THF and subsequent derivatization of the n-C-60 surface. These results for the first time demonstrate gamma-irradiation-mediated changes in the physico-chemical properties of THF-prepared nanocrystalline C-60, resulting in a complete loss of its cytotoxic effect and its conversion to a cytoprotective agent. (c) 2006 Elsevier Ltd. All rights reserved.",
journal = "Biomaterials",
title = "Inactivation of nanocrystalline C-60 cytotoxicity by gamma-irradiation",
volume = "27",
number = "29",
pages = "5049-5058",
doi = "10.1016/j.biomaterials.2006.05.047"
}

Isaković, A. J., Marković, Z. M., Nikolić, N. S., Todorović-Marković, B., Vranješ-Đurić, S., Harhaji, L. M., Raičević, N., Romčević, N. Ž., Vasiljević-Radović, D., Dramićanin, M.,& Trajković, V. S.. (2006). Inactivation of nanocrystalline C-60 cytotoxicity by gamma-irradiation. in Biomaterials, 27(29), 5049-5058.
https://doi.org/10.1016/j.biomaterials.2006.05.047

Isaković AJ, Marković ZM, Nikolić NS, Todorović-Marković B, Vranješ-Đurić S, Harhaji LM, Raičević N, Romčević NŽ, Vasiljević-Radović D, Dramićanin M, Trajković VS. Inactivation of nanocrystalline C-60 cytotoxicity by gamma-irradiation. in Biomaterials. 2006;27(29):5049-5058.
doi:10.1016/j.biomaterials.2006.05.047 .

Isaković, Aleksandra J., Marković, Zoran M., Nikolić, Nadežda S., Todorović-Marković, Biljana, Vranješ-Đurić, Sanja, Harhaji, Ljubica M., Raičević, Nevena, Romčević, Nebojša Ž., Vasiljević-Radović, Dana, Dramićanin, Miroslav, Trajković, Vladimir S., "Inactivation of nanocrystalline C-60 cytotoxicity by gamma-irradiation" in Biomaterials, 27, no. 29 (2006):5049-5058,
https://doi.org/10.1016/j.biomaterials.2006.05.047 . .

TY  - JOUR
AU  - Isaković, Aleksandra J.
AU  - Marković, Zoran M.
AU  - Todorović-Marković, Biljana
AU  - Nikolić, Nadežda S.
AU  - Vranješ-Đurić, Sanja
AU  - Mirković, Marija D.
AU  - Dramićanin, Miroslav
AU  - Harhaji, Ljubica M.
AU  - Raičević, Nevena
AU  - Nikolić, Zoran M.
AU  - Trajković, Vladimir S.
PY  - 2006
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3002
AB  - The mechanisms underlying the cytotoxic action of pure fullerene suspension (nano-C-60) and water-soluble polyhydroxylated fullerene [C-60(OH)(n)] were investigated. Crystal violet assay for cell viability demonstrated that nano-C-60 was at least three orders of magnitude more toxic than C-60(OH)(n) to mouse L929 fibrosarcoma, rat C6 glioma, and U251 human glioma cell lines. Flow cytometry analysis of cells stained with propidium iodide (PI), PI/annexin V-fluorescein isothiocyanate, or the redox-sensitive dye dihydrorhodamine revealed that nano-C-60 caused rapid (observable after few hours), reactive oxygen species (ROS)-associated necrosis characterized by cell membrane damage without DNA fragmentation. In contrast, C-60(OH)(n) caused delayed, ROS-independent cell death with characteristics of apoptosis, including DNA fragmentation and loss of cell membrane asymmetry in the absence of increased permeability. Accordingly, the antioxidant N-acetylcysteine protected the cell lines from nano-C-60 toxicity, but not C-60(OH)(n) toxicity, while the pan-caspase inhibitor z-VAD-fmk blocked C-60(OH)(n)-induced apoptosis, but not nano-C-60-mediated necrosis. Finally, C-60(OH)(n) antagonized, while nano-C-60 synergized with, the cytotoxic action of oxidative stress-inducing agents hydrogen peroxide and peroxynitrite donor 3-morpholinosydnonimine. Therefore, unlike polyhydroxylated C-60 that exerts mainly antioxidant/cytoprotective and only mild ROS-independent pro-apoptotic activity, pure crystalline C-60 seems to be endowed with strong pro-oxidant capacity responsible for the rapid necrotic cell death.
T2  - Toxicological Sciences
T1  - Distinct cytotoxic mechanisms of pristine versus hydroxylated fullerene
VL  - 91
IS  - 1
SP  - 173
EP  - 183
DO  - 10.1093/toxsci/kfj127
ER  - 

@article{
author = "Isaković, Aleksandra J. and Marković, Zoran M. and Todorović-Marković, Biljana and Nikolić, Nadežda S. and Vranješ-Đurić, Sanja and Mirković, Marija D. and Dramićanin, Miroslav and Harhaji, Ljubica M. and Raičević, Nevena and Nikolić, Zoran M. and Trajković, Vladimir S.",
year = "2006",
abstract = "The mechanisms underlying the cytotoxic action of pure fullerene suspension (nano-C-60) and water-soluble polyhydroxylated fullerene [C-60(OH)(n)] were investigated. Crystal violet assay for cell viability demonstrated that nano-C-60 was at least three orders of magnitude more toxic than C-60(OH)(n) to mouse L929 fibrosarcoma, rat C6 glioma, and U251 human glioma cell lines. Flow cytometry analysis of cells stained with propidium iodide (PI), PI/annexin V-fluorescein isothiocyanate, or the redox-sensitive dye dihydrorhodamine revealed that nano-C-60 caused rapid (observable after few hours), reactive oxygen species (ROS)-associated necrosis characterized by cell membrane damage without DNA fragmentation. In contrast, C-60(OH)(n) caused delayed, ROS-independent cell death with characteristics of apoptosis, including DNA fragmentation and loss of cell membrane asymmetry in the absence of increased permeability. Accordingly, the antioxidant N-acetylcysteine protected the cell lines from nano-C-60 toxicity, but not C-60(OH)(n) toxicity, while the pan-caspase inhibitor z-VAD-fmk blocked C-60(OH)(n)-induced apoptosis, but not nano-C-60-mediated necrosis. Finally, C-60(OH)(n) antagonized, while nano-C-60 synergized with, the cytotoxic action of oxidative stress-inducing agents hydrogen peroxide and peroxynitrite donor 3-morpholinosydnonimine. Therefore, unlike polyhydroxylated C-60 that exerts mainly antioxidant/cytoprotective and only mild ROS-independent pro-apoptotic activity, pure crystalline C-60 seems to be endowed with strong pro-oxidant capacity responsible for the rapid necrotic cell death.",
journal = "Toxicological Sciences",
title = "Distinct cytotoxic mechanisms of pristine versus hydroxylated fullerene",
volume = "91",
number = "1",
pages = "173-183",
doi = "10.1093/toxsci/kfj127"
}

Isaković, A. J., Marković, Z. M., Todorović-Marković, B., Nikolić, N. S., Vranješ-Đurić, S., Mirković, M. D., Dramićanin, M., Harhaji, L. M., Raičević, N., Nikolić, Z. M.,& Trajković, V. S.. (2006). Distinct cytotoxic mechanisms of pristine versus hydroxylated fullerene. in Toxicological Sciences, 91(1), 173-183.
https://doi.org/10.1093/toxsci/kfj127

Isaković AJ, Marković ZM, Todorović-Marković B, Nikolić NS, Vranješ-Đurić S, Mirković MD, Dramićanin M, Harhaji LM, Raičević N, Nikolić ZM, Trajković VS. Distinct cytotoxic mechanisms of pristine versus hydroxylated fullerene. in Toxicological Sciences. 2006;91(1):173-183.
doi:10.1093/toxsci/kfj127 .

Isaković, Aleksandra J., Marković, Zoran M., Todorović-Marković, Biljana, Nikolić, Nadežda S., Vranješ-Đurić, Sanja, Mirković, Marija D., Dramićanin, Miroslav, Harhaji, Ljubica M., Raičević, Nevena, Nikolić, Zoran M., Trajković, Vladimir S., "Distinct cytotoxic mechanisms of pristine versus hydroxylated fullerene" in Toxicological Sciences, 91, no. 1 (2006):173-183,
https://doi.org/10.1093/toxsci/kfj127 . .