TY  - JOUR
AU  - Mojic, Marija
AU  - Bogdanović Pristov, Jelena
AU  - Maksimović-Ivanić, Danijela
AU  - Jones, David R
AU  - Stanić, Marina
AU  - Mijatović, Sanja
AU  - Spasojević, Ivan
PY  - 2014
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/821
AB  - In vitro studies have shown that hydrogen peroxide (H2O2) produced by high-concentration ascorbate and cell culture medium iron efficiently kills cancer cells. This provided the rationale for clinical trials of high-dose intravenous ascorbate-based treatment for cancer. A drawback in all the in vitro studies was their failure to take into account the in vivo concentration of iron to supplement cell culture media which are characterized by low iron content. Here we showed, using two prostate cancer cell lines (LNCaP and PC-3) and primary astrocytes, that the anticancer/cytotoxic effects of ascorbate are completely abolished by iron at physiological concentrations in cell culture medium and human plasma. A detailed examination of mechanisms showed that iron at physiological concentrations promotes both production and decomposition of H2O2. The latter is mediated by Fenton reaction and prevents H2O2 accumulation. The hydroxyl radical, which is produced in the Fenton reaction, is buffered by extracellular proteins, and could not affect intracellular targets like H2O2. These findings show that anticancer effects of ascorbate have been significantly overestimated in previous in vitro studies, and that common cell culture media might be unsuitable for redox research.
PB  - Nature Publishing Group, London
T2  - Scientific Reports
T1  - Extracellular iron diminishes anticancer effects of vitamin C: An in vitro study
VL  - 4
DO  - 10.1038/srep05955
ER  - 

@article{
author = "Mojic, Marija and Bogdanović Pristov, Jelena and Maksimović-Ivanić, Danijela and Jones, David R and Stanić, Marina and Mijatović, Sanja and Spasojević, Ivan",
year = "2014",
abstract = "In vitro studies have shown that hydrogen peroxide (H2O2) produced by high-concentration ascorbate and cell culture medium iron efficiently kills cancer cells. This provided the rationale for clinical trials of high-dose intravenous ascorbate-based treatment for cancer. A drawback in all the in vitro studies was their failure to take into account the in vivo concentration of iron to supplement cell culture media which are characterized by low iron content. Here we showed, using two prostate cancer cell lines (LNCaP and PC-3) and primary astrocytes, that the anticancer/cytotoxic effects of ascorbate are completely abolished by iron at physiological concentrations in cell culture medium and human plasma. A detailed examination of mechanisms showed that iron at physiological concentrations promotes both production and decomposition of H2O2. The latter is mediated by Fenton reaction and prevents H2O2 accumulation. The hydroxyl radical, which is produced in the Fenton reaction, is buffered by extracellular proteins, and could not affect intracellular targets like H2O2. These findings show that anticancer effects of ascorbate have been significantly overestimated in previous in vitro studies, and that common cell culture media might be unsuitable for redox research.",
publisher = "Nature Publishing Group, London",
journal = "Scientific Reports",
title = "Extracellular iron diminishes anticancer effects of vitamin C: An in vitro study",
volume = "4",
doi = "10.1038/srep05955"
}

Mojic, M., Bogdanović Pristov, J., Maksimović-Ivanić, D., Jones, D. R., Stanić, M., Mijatović, S.,& Spasojević, I.. (2014). Extracellular iron diminishes anticancer effects of vitamin C: An in vitro study. in Scientific Reports
Nature Publishing Group, London., 4.
https://doi.org/10.1038/srep05955

Mojic M, Bogdanović Pristov J, Maksimović-Ivanić D, Jones DR, Stanić M, Mijatović S, Spasojević I. Extracellular iron diminishes anticancer effects of vitamin C: An in vitro study. in Scientific Reports. 2014;4.
doi:10.1038/srep05955 .

Mojic, Marija, Bogdanović Pristov, Jelena, Maksimović-Ivanić, Danijela, Jones, David R, Stanić, Marina, Mijatović, Sanja, Spasojević, Ivan, "Extracellular iron diminishes anticancer effects of vitamin C: An in vitro study" in Scientific Reports, 4 (2014),
https://doi.org/10.1038/srep05955 . .

TY  - JOUR
AU  - Spasojević, Ivan
AU  - Jones, David R
AU  - Andrades, Andmichael E
PY  - 2012
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/576
PB  - Hindawi Ltd, London
T2  - Oxidative Medicine and Cellular Longevity
T1  - Hydrogen Peroxide in Adaptation
VL  - 2012
DO  - 10.1155/2012/596019
ER  - 

@article{
author = "Spasojević, Ivan and Jones, David R and Andrades, Andmichael E",
year = "2012",
publisher = "Hindawi Ltd, London",
journal = "Oxidative Medicine and Cellular Longevity",
title = "Hydrogen Peroxide in Adaptation",
volume = "2012",
doi = "10.1155/2012/596019"
}

Spasojević, I., Jones, D. R.,& Andrades, A. E.. (2012). Hydrogen Peroxide in Adaptation. in Oxidative Medicine and Cellular Longevity
Hindawi Ltd, London., 2012.
https://doi.org/10.1155/2012/596019

Spasojević I, Jones DR, Andrades AE. Hydrogen Peroxide in Adaptation. in Oxidative Medicine and Cellular Longevity. 2012;2012.
doi:10.1155/2012/596019 .

Spasojević, Ivan, Jones, David R, Andrades, Andmichael E, "Hydrogen Peroxide in Adaptation" in Oxidative Medicine and Cellular Longevity, 2012 (2012),
https://doi.org/10.1155/2012/596019 . .

TY  - JOUR
AU  - Bajić, Aleksandar
AU  - Zakrzewska, Joanna
AU  - Godjevac, Dejan M
AU  - Andjus, Pavle R.
AU  - Jones, David R
AU  - Spasić, Mihajlo
AU  - Spasojević, Ivan
PY  - 2011
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/484
AB  - The cytoprotective activity of F16BP has been documented in severe conditions such as convulsions, reperfusion injury, septic shock, diabetic complications, hypothermia-induced injury, UV-provoked skin damage and in other processes including apoptosis and excitotoxicity. F16BP shows very efficient cytoprotective activity in astroglial cells exposed to H2O2-provoked oxidative stress and during neuronal injury caused by hypoxic conditions. As most of the aforementioned processes involve iron activity-related conditions, we investigated the ferric and ferrous iron binding properties of F16BP under physiological conditions using P-31 NMR and EPR spectroscopy. Our results indicate that cytoprotective F16BP activity is predominantly based on ferrous iron sequestration. P-31 NMR spectroscopy of F16BP employing paramagnetic properties of iron clearly showed that F16BP forms stabile complexes with Fe2+ which was verified by EPR of another divalent cation-Mn2+. On the other hand, F16BP does not sequester ferric iron nor does it increase its redox activity as shown by P-31 NMR and EPR spin-trapping. Therefore, F16BP may be beneficial in neurodegenerative and other conditions that are characterised by ferric iron stores and deposits.
PB  - Elsevier Sci Ltd, Oxford
T2  - Carbohydrate Research
T1  - Relevance of the ability of fructose 1,6-bis(phosphate) to sequester ferrous but not ferric ions
EP  - 420
IS  - 3
SP  - 416
VL  - 346
DO  - 10.1016/j.carres.2010.12.008
ER  - 

@article{
author = "Bajić, Aleksandar and Zakrzewska, Joanna and Godjevac, Dejan M and Andjus, Pavle R. and Jones, David R and Spasić, Mihajlo and Spasojević, Ivan",
year = "2011",
abstract = "The cytoprotective activity of F16BP has been documented in severe conditions such as convulsions, reperfusion injury, septic shock, diabetic complications, hypothermia-induced injury, UV-provoked skin damage and in other processes including apoptosis and excitotoxicity. F16BP shows very efficient cytoprotective activity in astroglial cells exposed to H2O2-provoked oxidative stress and during neuronal injury caused by hypoxic conditions. As most of the aforementioned processes involve iron activity-related conditions, we investigated the ferric and ferrous iron binding properties of F16BP under physiological conditions using P-31 NMR and EPR spectroscopy. Our results indicate that cytoprotective F16BP activity is predominantly based on ferrous iron sequestration. P-31 NMR spectroscopy of F16BP employing paramagnetic properties of iron clearly showed that F16BP forms stabile complexes with Fe2+ which was verified by EPR of another divalent cation-Mn2+. On the other hand, F16BP does not sequester ferric iron nor does it increase its redox activity as shown by P-31 NMR and EPR spin-trapping. Therefore, F16BP may be beneficial in neurodegenerative and other conditions that are characterised by ferric iron stores and deposits.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Carbohydrate Research",
title = "Relevance of the ability of fructose 1,6-bis(phosphate) to sequester ferrous but not ferric ions",
pages = "420-416",
number = "3",
volume = "346",
doi = "10.1016/j.carres.2010.12.008"
}

Bajić, A., Zakrzewska, J., Godjevac, D. M., Andjus, P. R., Jones, D. R., Spasić, M.,& Spasojević, I.. (2011). Relevance of the ability of fructose 1,6-bis(phosphate) to sequester ferrous but not ferric ions. in Carbohydrate Research
Elsevier Sci Ltd, Oxford., 346(3), 416-420.
https://doi.org/10.1016/j.carres.2010.12.008

Bajić A, Zakrzewska J, Godjevac DM, Andjus PR, Jones DR, Spasić M, Spasojević I. Relevance of the ability of fructose 1,6-bis(phosphate) to sequester ferrous but not ferric ions. in Carbohydrate Research. 2011;346(3):416-420.
doi:10.1016/j.carres.2010.12.008 .

Bajić, Aleksandar, Zakrzewska, Joanna, Godjevac, Dejan M, Andjus, Pavle R., Jones, David R, Spasić, Mihajlo, Spasojević, Ivan, "Relevance of the ability of fructose 1,6-bis(phosphate) to sequester ferrous but not ferric ions" in Carbohydrate Research, 346, no. 3 (2011):416-420,
https://doi.org/10.1016/j.carres.2010.12.008 . .

TY  - JOUR
AU  - Spasojević, Ivan
AU  - Mojović, Miloš
AU  - Stević, Zorica D
AU  - Spasic, Snežana D
AU  - Jones, David R
AU  - Morina, Arian
AU  - Spasić, Mihajlo
PY  - 2010
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/417
AB  - A breakdown in homeostasis of redox-active metals represents an important factor for neurodegeneration. We have used EPR spectroscopy and BMPO spin-trap to investigate the catalytic properties and ligand modulation of redox activity of copper and iron in human cerebrospinal fluid (CSF). In contrast to iron, copper supplementation provoked a statistically significant increase in hydroxyl free radical generation in CSF treated with H(2)O(2). However, in a binary copper/iron containing Fenton system, iron catalytically activated copper. The chelator EDTA, which represents a model of physiological metal ligands, completely prevented copper's redox activity in CSF, while iron chelation led to a significant increase in hydroxyl radical generation, indicating that copper and iron do not only have diverse catalytic properties in the CSF but also that their redox activities are differently modulated by ligands. The application of DDC reduced hydroxyl radical generation in the CSF containing catalytically active metals (free Cu(2+) or Fe(3+)-EDTA complex). We conclude that chelators, such as DDC, are capable of preventing the pro-oxidative activity of both metals and may be suitable for reducing hydroxyl radical formation in certain pathophysiological settings.
PB  - Maney Publishing, Leeds
T2  - Redox Report
T1  - Bioavailability and catalytic properties of copper and iron for Fenton chemistry in human cerebrospinal fluid
EP  - 35
IS  - 1
SP  - 29
VL  - 15
DO  - 10.1179/174329210X12650506623087
ER  - 

@article{
author = "Spasojević, Ivan and Mojović, Miloš and Stević, Zorica D and Spasic, Snežana D and Jones, David R and Morina, Arian and Spasić, Mihajlo",
year = "2010",
abstract = "A breakdown in homeostasis of redox-active metals represents an important factor for neurodegeneration. We have used EPR spectroscopy and BMPO spin-trap to investigate the catalytic properties and ligand modulation of redox activity of copper and iron in human cerebrospinal fluid (CSF). In contrast to iron, copper supplementation provoked a statistically significant increase in hydroxyl free radical generation in CSF treated with H(2)O(2). However, in a binary copper/iron containing Fenton system, iron catalytically activated copper. The chelator EDTA, which represents a model of physiological metal ligands, completely prevented copper's redox activity in CSF, while iron chelation led to a significant increase in hydroxyl radical generation, indicating that copper and iron do not only have diverse catalytic properties in the CSF but also that their redox activities are differently modulated by ligands. The application of DDC reduced hydroxyl radical generation in the CSF containing catalytically active metals (free Cu(2+) or Fe(3+)-EDTA complex). We conclude that chelators, such as DDC, are capable of preventing the pro-oxidative activity of both metals and may be suitable for reducing hydroxyl radical formation in certain pathophysiological settings.",
publisher = "Maney Publishing, Leeds",
journal = "Redox Report",
title = "Bioavailability and catalytic properties of copper and iron for Fenton chemistry in human cerebrospinal fluid",
pages = "35-29",
number = "1",
volume = "15",
doi = "10.1179/174329210X12650506623087"
}

Spasojević, I., Mojović, M., Stević, Z. D., Spasic, S. D., Jones, D. R., Morina, A.,& Spasić, M.. (2010). Bioavailability and catalytic properties of copper and iron for Fenton chemistry in human cerebrospinal fluid. in Redox Report
Maney Publishing, Leeds., 15(1), 29-35.
https://doi.org/10.1179/174329210X12650506623087

Spasojević I, Mojović M, Stević ZD, Spasic SD, Jones DR, Morina A, Spasić M. Bioavailability and catalytic properties of copper and iron for Fenton chemistry in human cerebrospinal fluid. in Redox Report. 2010;15(1):29-35.
doi:10.1179/174329210X12650506623087 .

Spasojević, Ivan, Mojović, Miloš, Stević, Zorica D, Spasic, Snežana D, Jones, David R, Morina, Arian, Spasić, Mihajlo, "Bioavailability and catalytic properties of copper and iron for Fenton chemistry in human cerebrospinal fluid" in Redox Report, 15, no. 1 (2010):29-35,
https://doi.org/10.1179/174329210X12650506623087 . .

TY  - JOUR
AU  - Spasojević, Ivan
AU  - Stević, Zorica D
AU  - Nikolić-Kokić, Aleksandra
AU  - Jones, David R
AU  - Blagojević, Duško P
AU  - Spasić, Mihajlo
PY  - 2010
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/410
AB  - Ferrous iron, released from iron deposits in the motor cortex and other brain regions of amyotrophic lateral sclerosis (ALS) patients, participates in the Fenton reaction in cerebrospinal fluid (CSF) alongside H2O2, which is continuously released by neuronal cells. In vivo, the production of notoriously reactive hydroxyl radicals via this reaction could lead to the progression of the disease. Herein, we have examined the effect of ascorbate and uric acid on the production of hydroxyl radicals in CSF from both sporadic ALS patients and control subjects. Electron paramagnetic resonance spectroscopy identified ascorbyl radicals in CSF from ALS patients whereas it was undetectable in control CSF. The addition of H2O2 to the CSF from ALS patients provoked further formation of ascorbyl radicals and the formation of hydroxyl radicals ex vivo. The hydroxyl addition of uric acid to CSF from ALS patients diminished the production of hydroxyl radicals. In conclusion, there are clear differences between the roles of the two examined radical scavengers in the CSF of ALS patients indicating that the use of ascorbate could have unfavourable effects in ALS patients.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Redox Report
T1  - Different roles of radical scavengers - ascorbate and urate in the cerebrospinal fluid of amyotrophic lateral sclerosis patients
EP  - 86
IS  - 2
SP  - 81
VL  - 15
DO  - 10.1179/174329210X12650506623320
ER  - 

@article{
author = "Spasojević, Ivan and Stević, Zorica D and Nikolić-Kokić, Aleksandra and Jones, David R and Blagojević, Duško P and Spasić, Mihajlo",
year = "2010",
abstract = "Ferrous iron, released from iron deposits in the motor cortex and other brain regions of amyotrophic lateral sclerosis (ALS) patients, participates in the Fenton reaction in cerebrospinal fluid (CSF) alongside H2O2, which is continuously released by neuronal cells. In vivo, the production of notoriously reactive hydroxyl radicals via this reaction could lead to the progression of the disease. Herein, we have examined the effect of ascorbate and uric acid on the production of hydroxyl radicals in CSF from both sporadic ALS patients and control subjects. Electron paramagnetic resonance spectroscopy identified ascorbyl radicals in CSF from ALS patients whereas it was undetectable in control CSF. The addition of H2O2 to the CSF from ALS patients provoked further formation of ascorbyl radicals and the formation of hydroxyl radicals ex vivo. The hydroxyl addition of uric acid to CSF from ALS patients diminished the production of hydroxyl radicals. In conclusion, there are clear differences between the roles of the two examined radical scavengers in the CSF of ALS patients indicating that the use of ascorbate could have unfavourable effects in ALS patients.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Redox Report",
title = "Different roles of radical scavengers - ascorbate and urate in the cerebrospinal fluid of amyotrophic lateral sclerosis patients",
pages = "86-81",
number = "2",
volume = "15",
doi = "10.1179/174329210X12650506623320"
}

Spasojević, I., Stević, Z. D., Nikolić-Kokić, A., Jones, D. R., Blagojević, D. P.,& Spasić, M.. (2010). Different roles of radical scavengers - ascorbate and urate in the cerebrospinal fluid of amyotrophic lateral sclerosis patients. in Redox Report
Taylor & Francis Ltd, Abingdon., 15(2), 81-86.
https://doi.org/10.1179/174329210X12650506623320

Spasojević I, Stević ZD, Nikolić-Kokić A, Jones DR, Blagojević DP, Spasić M. Different roles of radical scavengers - ascorbate and urate in the cerebrospinal fluid of amyotrophic lateral sclerosis patients. in Redox Report. 2010;15(2):81-86.
doi:10.1179/174329210X12650506623320 .

Spasojević, Ivan, Stević, Zorica D, Nikolić-Kokić, Aleksandra, Jones, David R, Blagojević, Duško P, Spasić, Mihajlo, "Different roles of radical scavengers - ascorbate and urate in the cerebrospinal fluid of amyotrophic lateral sclerosis patients" in Redox Report, 15, no. 2 (2010):81-86,
https://doi.org/10.1179/174329210X12650506623320 . .

TY  - JOUR
AU  - Spasojević, Ivan
AU  - Mojović, Miloš
AU  - Blagojević, Duško
AU  - Spasic, Snežana D.
AU  - Jones, David R
AU  - Nikolić-Kokić, Aleksandra
AU  - Spasić, Mihajlo
PY  - 2009
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/321
AB  - The hydroxyl radical ((OH)-O-center dot) has detrimental biological activity due to its very high reactivity. Our experiments were designed to determine the effects of equimolar concentrations of glucose, fructose and mannitol and three phosphorylated forms of fructose (fructose-1-phosphate (F1P): fructose-6-phosphate (F6P): and fructose-1,6-bis(phosphate) (F16BP)) on (OH)-O-center dot radical production via the Fenton reaction. EPR spectroscopy using spin-trap DEPMPO was applied to detect radical production. We found that the percentage inhibition of (OH)-O-center dot radical formation decreased in the order F16BP > F1P > F6P > fructose > mannitol = glucose. As ketoses can sequester redox-active iron thus preventing the Fenton reaction, the Haber-Weiss-like system was also employed to generate (OH)-O-center dot, so that the effect of iron sequestration could be distinguished from direct (OH)-O-center dot radical scavenging. In the latter system, the rank order of (OH)-O-center dot scavenging activity was F16BP > F1P > F6P > fructose = mannitol = glucose. Our results clearly demonstrate that intracellular phosphorylated forms of fructose have more scavenging properties than fructose or glucose, leading us to conclude that the acute administration of fructose could overcome the body's reaction to exogenous antioxidants during appropriate therapy in certain pathophysiological conditions related to oxidative stress, Such as sepsis, neurodegenerative diseases, atherosclerosis, malignancy, and some complications of pregnancy.
PB  - Elsevier Sci Ltd, Oxford
T2  - Carbohydrate Research
T1  - Relevance of the capacity of phosphorylated fructose to scavenge the hydroxyl radical
EP  - 84
IS  - 1
SP  - 80
VL  - 344
DO  - 10.1016/j.carres.2008.09.025
ER  - 

@article{
author = "Spasojević, Ivan and Mojović, Miloš and Blagojević, Duško and Spasic, Snežana D. and Jones, David R and Nikolić-Kokić, Aleksandra and Spasić, Mihajlo",
year = "2009",
abstract = "The hydroxyl radical ((OH)-O-center dot) has detrimental biological activity due to its very high reactivity. Our experiments were designed to determine the effects of equimolar concentrations of glucose, fructose and mannitol and three phosphorylated forms of fructose (fructose-1-phosphate (F1P): fructose-6-phosphate (F6P): and fructose-1,6-bis(phosphate) (F16BP)) on (OH)-O-center dot radical production via the Fenton reaction. EPR spectroscopy using spin-trap DEPMPO was applied to detect radical production. We found that the percentage inhibition of (OH)-O-center dot radical formation decreased in the order F16BP > F1P > F6P > fructose > mannitol = glucose. As ketoses can sequester redox-active iron thus preventing the Fenton reaction, the Haber-Weiss-like system was also employed to generate (OH)-O-center dot, so that the effect of iron sequestration could be distinguished from direct (OH)-O-center dot radical scavenging. In the latter system, the rank order of (OH)-O-center dot scavenging activity was F16BP > F1P > F6P > fructose = mannitol = glucose. Our results clearly demonstrate that intracellular phosphorylated forms of fructose have more scavenging properties than fructose or glucose, leading us to conclude that the acute administration of fructose could overcome the body's reaction to exogenous antioxidants during appropriate therapy in certain pathophysiological conditions related to oxidative stress, Such as sepsis, neurodegenerative diseases, atherosclerosis, malignancy, and some complications of pregnancy.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Carbohydrate Research",
title = "Relevance of the capacity of phosphorylated fructose to scavenge the hydroxyl radical",
pages = "84-80",
number = "1",
volume = "344",
doi = "10.1016/j.carres.2008.09.025"
}

Spasojević, I., Mojović, M., Blagojević, D., Spasic, S. D., Jones, D. R., Nikolić-Kokić, A.,& Spasić, M.. (2009). Relevance of the capacity of phosphorylated fructose to scavenge the hydroxyl radical. in Carbohydrate Research
Elsevier Sci Ltd, Oxford., 344(1), 80-84.
https://doi.org/10.1016/j.carres.2008.09.025

Spasojević I, Mojović M, Blagojević D, Spasic SD, Jones DR, Nikolić-Kokić A, Spasić M. Relevance of the capacity of phosphorylated fructose to scavenge the hydroxyl radical. in Carbohydrate Research. 2009;344(1):80-84.
doi:10.1016/j.carres.2008.09.025 .

Spasojević, Ivan, Mojović, Miloš, Blagojević, Duško, Spasic, Snežana D., Jones, David R, Nikolić-Kokić, Aleksandra, Spasić, Mihajlo, "Relevance of the capacity of phosphorylated fructose to scavenge the hydroxyl radical" in Carbohydrate Research, 344, no. 1 (2009):80-84,
https://doi.org/10.1016/j.carres.2008.09.025 . .