TY  - JOUR
AU  - Spasojević, Ivan B
AU  - Morina, Arian
AU  - Mojović, Milos D
AU  - Stević, Zorica D
AU  - Spasić, Snezana D
AU  - Jones, David R
AU  - Spasić, Mihajlo
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1405
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.
T2  - Redox Report
T1  - Bioavailability and catalytic properties of copper and iron for Fenton chemistry in human cerebrospinal fluid
IS  - 1
VL  - 15
EP  - 35
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1405
ER  - 

@article{
author = "Spasojević, Ivan B and Morina, Arian and Mojović, Milos D and Stević, Zorica D and Spasić, Snezana D and Jones, David R 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.",
journal = "Redox Report",
title = "Bioavailability and catalytic properties of copper and iron for Fenton chemistry in human cerebrospinal fluid",
number = "1",
volume = "15",
pages = "35",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1405"
}

Spasojević, I. B., Morina, A., Mojović, M. D., Stević, Z. D., Spasić, S. D., Jones, D. R.,& Spasić, M.. (2010). Bioavailability and catalytic properties of copper and iron for Fenton chemistry in human cerebrospinal fluid. in Redox Report, 15(1).
https://hdl.handle.net/21.15107/rcub_ibiss_1405

Spasojević IB, Morina A, Mojović MD, Stević ZD, Spasić SD, Jones DR, Spasić M. Bioavailability and catalytic properties of copper and iron for Fenton chemistry in human cerebrospinal fluid. in Redox Report. 2010;15(1):null-35.
https://hdl.handle.net/21.15107/rcub_ibiss_1405 .

Spasojević, Ivan B, Morina, Arian, Mojović, Milos D, Stević, Zorica D, Spasić, Snezana D, Jones, David R, Spasić, Mihajlo, "Bioavailability and catalytic properties of copper and iron for Fenton chemistry in human cerebrospinal fluid" in Redox Report, 15, no. 1 (2010),
https://hdl.handle.net/21.15107/rcub_ibiss_1405 .

TY  - JOUR
AU  - Miljević, Cedo D
AU  - Nikolić-Kokić, Aleksandra
AU  - Saičić, Zorica
AU  - Milosavljević, Maja
AU  - Blagojević, Duško
AU  - Lecić-Tosevski, Dusica M
AU  - Jones, David R
AU  - Spasić, Mihajlo
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1365
AB  - The activities of antioxidant defence enzymes were determined in erythrocytes isolated from types I and II schizophrenic male patients and from healthy controls. Significant differences in superoxide dismutase (SOD) activity (type I: 3284 +/- 577; type II: 2959 +/- 697 compared with controls: 3778 +/- 577; analysis of variance (ANOVA) P<0.001), catalase (CAT) activity (type I: 17.8 +/- 1.8 compared to type II: 19.2 +/- 1.5 and both compared with controls: 19.2 +/- 1.5; ANOVA P<0.05). glutathione peroxidase (GSH-Px) activity (controls: 17.8 +/- 2.3; type I: 13.9 +/- 2.9 and type II: 11.6 +/- 1.9; ANOVA P<0.001) as well as in glutathione reductase (GR) activity (controls: 5.0 +/- 0.8; type I: 4.3 +/- 0.9 and type II: 4.5 +/- 0.8; ANOVA P<0.01) were apparent. Correlation analysis of antioxidant defence enzymes showed significant negative correlation between GSH-Px and CAT activities (P<0.01) in type I patients. In type II patients, GSH-Px activity was significantly positively correlated with GR (P<0.01). Canonical discriminant analysis separated type I and type II patients from controls (and among each other) with a high degree of certainty according to the overall group composition of antioxidant defence enzymes. Our results indicate differences in the composition of antioxidant defence between controls and antipsychotic treated type I and type II patients with a possible negative feedback influence on the pathological process, which could provide a rationale for applying antioxidants during schizophrenic therapy. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
T2  - Psychiatry Research
T1  - Correlation analysis confirms differences in antioxidant defence in the blood of types I and II schizophrenic male patients treated with anti-psychotic medication
IS  - 1
VL  - 178
EP  - 72
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1365
ER  - 

@article{
author = "Miljević, Cedo D and Nikolić-Kokić, Aleksandra and Saičić, Zorica and Milosavljević, Maja and Blagojević, Duško and Lecić-Tosevski, Dusica M and Jones, David R and Spasić, Mihajlo",
year = "2010",
abstract = "The activities of antioxidant defence enzymes were determined in erythrocytes isolated from types I and II schizophrenic male patients and from healthy controls. Significant differences in superoxide dismutase (SOD) activity (type I: 3284 +/- 577; type II: 2959 +/- 697 compared with controls: 3778 +/- 577; analysis of variance (ANOVA) P<0.001), catalase (CAT) activity (type I: 17.8 +/- 1.8 compared to type II: 19.2 +/- 1.5 and both compared with controls: 19.2 +/- 1.5; ANOVA P<0.05). glutathione peroxidase (GSH-Px) activity (controls: 17.8 +/- 2.3; type I: 13.9 +/- 2.9 and type II: 11.6 +/- 1.9; ANOVA P<0.001) as well as in glutathione reductase (GR) activity (controls: 5.0 +/- 0.8; type I: 4.3 +/- 0.9 and type II: 4.5 +/- 0.8; ANOVA P<0.01) were apparent. Correlation analysis of antioxidant defence enzymes showed significant negative correlation between GSH-Px and CAT activities (P<0.01) in type I patients. In type II patients, GSH-Px activity was significantly positively correlated with GR (P<0.01). Canonical discriminant analysis separated type I and type II patients from controls (and among each other) with a high degree of certainty according to the overall group composition of antioxidant defence enzymes. Our results indicate differences in the composition of antioxidant defence between controls and antipsychotic treated type I and type II patients with a possible negative feedback influence on the pathological process, which could provide a rationale for applying antioxidants during schizophrenic therapy. (C) 2009 Elsevier Ireland Ltd. All rights reserved.",
journal = "Psychiatry Research",
title = "Correlation analysis confirms differences in antioxidant defence in the blood of types I and II schizophrenic male patients treated with anti-psychotic medication",
number = "1",
volume = "178",
pages = "72",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1365"
}

Miljević, C. D., Nikolić-Kokić, A., Saičić, Z., Milosavljević, M., Blagojević, D., Lecić-Tosevski, D. M., Jones, D. R.,& Spasić, M.. (2010). Correlation analysis confirms differences in antioxidant defence in the blood of types I and II schizophrenic male patients treated with anti-psychotic medication. in Psychiatry Research, 178(1).
https://hdl.handle.net/21.15107/rcub_ibiss_1365

Miljević CD, Nikolić-Kokić A, Saičić Z, Milosavljević M, Blagojević D, Lecić-Tosevski DM, Jones DR, Spasić M. Correlation analysis confirms differences in antioxidant defence in the blood of types I and II schizophrenic male patients treated with anti-psychotic medication. in Psychiatry Research. 2010;178(1):null-72.
https://hdl.handle.net/21.15107/rcub_ibiss_1365 .

Miljević, Cedo D, Nikolić-Kokić, Aleksandra, Saičić, Zorica, Milosavljević, Maja, Blagojević, Duško, Lecić-Tosevski, Dusica M, Jones, David R, Spasić, Mihajlo, "Correlation analysis confirms differences in antioxidant defence in the blood of types I and II schizophrenic male patients treated with anti-psychotic medication" in Psychiatry Research, 178, no. 1 (2010),
https://hdl.handle.net/21.15107/rcub_ibiss_1365 .

TY  - JOUR
AU  - Miljević, Cedo D
AU  - Nikolić, Milan R
AU  - Nikolić-Kokić, Aleksandra
AU  - Jones, David R
AU  - Niketić, Vesna P
AU  - Lecić-Tosevski, Dusica M
AU  - Spasić, Mihajlo
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1395
AB  - Objective: Despite clozapine's unique effectiveness in patients with schizophrenia, a number of adverse effects have been recognised including abnormalities in lipid and glucose metabolisms. A high clozapine level in red blood cells (RBCs) and disturbed anti-oxidant enzyme activities in blood from schizophrenic patients prompted us to investigate lipid status and anti-oxidant enzyme defence in the blood of chronic schizophrenic patients on long-term clozapine therapy. Methods: Plasma lipids, RBC anti-oxidant enzyme activities and haemoglobin (Hb) content were measured using established procedures in a group of eighteen chronically-medicated (average 630 days of therapy) schizophrenic patients receiving clozapine (average dose of 295 mg/day) and data were compared with those from a group of eighteen well-matched normal controls. Results: Significantly higher levels of plasma triglycerides (by 47%, p<0.01) and total cholesterol and phospholipids (by 8% and 11%, respectively p<0.05) in patients were found. CuZn-superoxide dismutase (SOD1) activity was markedly higher (by 35%, p<0.001) while selenium-dependent glutathione peroxidase (GSH-Px1) activity was markedly lower (by 41%, p<0.001) in patients. In addition, metHb and HbA1c levels in patients were significantly higher (by 58% and 25%. respectively p<0.001). SOD1 activity was negatively correlated (p<0.001) to GSH-Px1 activity in patients. Conclusions:The findings support the view that ongoing oxidative stress may be a mechanism by which clozapine induces some adverse effects that increase the risk of diabetes and metabolic syndrome. If valid, this would indicate that in parallel with long-term clozapine treatment, schizophrenic patients could be encouraged to make some lifestyle changes to limit the detrimental effects of the medication. (C) 2009 Elsevier Inc. All rights reserved.
T2  - Progress in Neuro-Psychopharmacology & Biological Psychiatry
T1  - Lipid status, anti-oxidant enzyme defence and haemoglobin content in the blood of long-term clozapine-treated schizophrenic patients
IS  - 2
VL  - 34
EP  - 307
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1395
ER  - 

@article{
author = "Miljević, Cedo D and Nikolić, Milan R and Nikolić-Kokić, Aleksandra and Jones, David R and Niketić, Vesna P and Lecić-Tosevski, Dusica M and Spasić, Mihajlo",
year = "2010",
abstract = "Objective: Despite clozapine's unique effectiveness in patients with schizophrenia, a number of adverse effects have been recognised including abnormalities in lipid and glucose metabolisms. A high clozapine level in red blood cells (RBCs) and disturbed anti-oxidant enzyme activities in blood from schizophrenic patients prompted us to investigate lipid status and anti-oxidant enzyme defence in the blood of chronic schizophrenic patients on long-term clozapine therapy. Methods: Plasma lipids, RBC anti-oxidant enzyme activities and haemoglobin (Hb) content were measured using established procedures in a group of eighteen chronically-medicated (average 630 days of therapy) schizophrenic patients receiving clozapine (average dose of 295 mg/day) and data were compared with those from a group of eighteen well-matched normal controls. Results: Significantly higher levels of plasma triglycerides (by 47%, p<0.01) and total cholesterol and phospholipids (by 8% and 11%, respectively p<0.05) in patients were found. CuZn-superoxide dismutase (SOD1) activity was markedly higher (by 35%, p<0.001) while selenium-dependent glutathione peroxidase (GSH-Px1) activity was markedly lower (by 41%, p<0.001) in patients. In addition, metHb and HbA1c levels in patients were significantly higher (by 58% and 25%. respectively p<0.001). SOD1 activity was negatively correlated (p<0.001) to GSH-Px1 activity in patients. Conclusions:The findings support the view that ongoing oxidative stress may be a mechanism by which clozapine induces some adverse effects that increase the risk of diabetes and metabolic syndrome. If valid, this would indicate that in parallel with long-term clozapine treatment, schizophrenic patients could be encouraged to make some lifestyle changes to limit the detrimental effects of the medication. (C) 2009 Elsevier Inc. All rights reserved.",
journal = "Progress in Neuro-Psychopharmacology & Biological Psychiatry",
title = "Lipid status, anti-oxidant enzyme defence and haemoglobin content in the blood of long-term clozapine-treated schizophrenic patients",
number = "2",
volume = "34",
pages = "307",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1395"
}

Miljević, C. D., Nikolić, M. R., Nikolić-Kokić, A., Jones, D. R., Niketić, V. P., Lecić-Tosevski, D. M.,& Spasić, M.. (2010). Lipid status, anti-oxidant enzyme defence and haemoglobin content in the blood of long-term clozapine-treated schizophrenic patients. in Progress in Neuro-Psychopharmacology & Biological Psychiatry, 34(2).
https://hdl.handle.net/21.15107/rcub_ibiss_1395

Miljević CD, Nikolić MR, Nikolić-Kokić A, Jones DR, Niketić VP, Lecić-Tosevski DM, Spasić M. Lipid status, anti-oxidant enzyme defence and haemoglobin content in the blood of long-term clozapine-treated schizophrenic patients. in Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2010;34(2):null-307.
https://hdl.handle.net/21.15107/rcub_ibiss_1395 .

Miljević, Cedo D, Nikolić, Milan R, Nikolić-Kokić, Aleksandra, Jones, David R, Niketić, Vesna P, Lecić-Tosevski, Dusica M, Spasić, Mihajlo, "Lipid status, anti-oxidant enzyme defence and haemoglobin content in the blood of long-term clozapine-treated schizophrenic patients" in Progress in Neuro-Psychopharmacology & Biological Psychiatry, 34, no. 2 (2010),
https://hdl.handle.net/21.15107/rcub_ibiss_1395 .

TY  - JOUR
AU  - Spasojević, Ivan B
AU  - Stević, Zorica D
AU  - Nikolić-Kokić, Aleksandra
AU  - Jones, David R
AU  - Blagojević, Duško
AU  - Spasić, Mihajlo
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1392
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 H(2)O(2), 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 H(2)O(2) 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.
T2  - Redox Report
T1  - Different roles of radical scavengers - ascorbate and urate in the cerebrospinal fluid of amyotrophic lateral sclerosis patients
IS  - 2
VL  - 15
EP  - 86
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1392
ER  - 

@article{
author = "Spasojević, Ivan B and Stević, Zorica D and Nikolić-Kokić, Aleksandra and Jones, David R and Blagojević, Duško 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 H(2)O(2), 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 H(2)O(2) 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.",
journal = "Redox Report",
title = "Different roles of radical scavengers - ascorbate and urate in the cerebrospinal fluid of amyotrophic lateral sclerosis patients",
number = "2",
volume = "15",
pages = "86",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1392"
}

Spasojević, I. B., Stević, Z. D., Nikolić-Kokić, A., Jones, D. R., Blagojević, D.,& Spasić, M.. (2010). Different roles of radical scavengers - ascorbate and urate in the cerebrospinal fluid of amyotrophic lateral sclerosis patients. in Redox Report, 15(2).
https://hdl.handle.net/21.15107/rcub_ibiss_1392

Spasojević IB, Stević ZD, Nikolić-Kokić A, Jones DR, Blagojević D, 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):null-86.
https://hdl.handle.net/21.15107/rcub_ibiss_1392 .

Spasojević, Ivan B, Stević, Zorica D, Nikolić-Kokić, Aleksandra, Jones, David R, Blagojević, Duško, 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),
https://hdl.handle.net/21.15107/rcub_ibiss_1392 .

TY  - JOUR
AU  - Oreščanin Dušić, Zorana
AU  - Milovanović, Slobodan R
AU  - Spasić, Snezana D
AU  - Jones, David R
AU  - Spasić, Mihajlo
PY  - 2007
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1605
AB  - The conversion of nitric oxide (NO*) into its congeners nitrosonium (NO+) and nitroxyl (HNO/NO-) ions may have important consequences for signal transduction and physiological responses. Manganese-containing superoxide dismutase (MnSOD) may convert NO* into its redox congeners. In our current work, we have examined the mechanism of sodium nitroprusside (SNP)-induced relaxation of arteries, with or without endothelium, from both normotensive and spontaneously hypertensive (SH) rats in the absence and presence of MnSOD. SNP induced a greater degree of relaxation in normotensive than in SH rats. MnSOD antagonized SNPinduced relaxation and effect was greater in normotensive than hypertensive rats. However, MnSOD even potentiated SNP-induced relaxation in mesenteric arteries with endothelium from SH rats. Our results indicate that HNO/NO--mediated relaxation is more effective in mesenteric artery smooth muscle from SH rats than from normotensive rats and that vascular dysfunction in SH rats is not solely endothelium-derived but involves changes in vascular smooth muscles.
T2  - Pharmacological Reports
T1  - Different responses of mesenteric artery from normotensive and spontaneously hypertensive rats to nitric oxide and its redox congeners
IS  - 3
VL  - 59
EP  - 322
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1605
ER  - 

@article{
author = "Oreščanin Dušić, Zorana and Milovanović, Slobodan R and Spasić, Snezana D and Jones, David R and Spasić, Mihajlo",
year = "2007",
abstract = "The conversion of nitric oxide (NO*) into its congeners nitrosonium (NO+) and nitroxyl (HNO/NO-) ions may have important consequences for signal transduction and physiological responses. Manganese-containing superoxide dismutase (MnSOD) may convert NO* into its redox congeners. In our current work, we have examined the mechanism of sodium nitroprusside (SNP)-induced relaxation of arteries, with or without endothelium, from both normotensive and spontaneously hypertensive (SH) rats in the absence and presence of MnSOD. SNP induced a greater degree of relaxation in normotensive than in SH rats. MnSOD antagonized SNPinduced relaxation and effect was greater in normotensive than hypertensive rats. However, MnSOD even potentiated SNP-induced relaxation in mesenteric arteries with endothelium from SH rats. Our results indicate that HNO/NO--mediated relaxation is more effective in mesenteric artery smooth muscle from SH rats than from normotensive rats and that vascular dysfunction in SH rats is not solely endothelium-derived but involves changes in vascular smooth muscles.",
journal = "Pharmacological Reports",
title = "Different responses of mesenteric artery from normotensive and spontaneously hypertensive rats to nitric oxide and its redox congeners",
number = "3",
volume = "59",
pages = "322",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1605"
}

Oreščanin Dušić, Z., Milovanović, S. R., Spasić, S. D., Jones, D. R.,& Spasić, M.. (2007). Different responses of mesenteric artery from normotensive and spontaneously hypertensive rats to nitric oxide and its redox congeners. in Pharmacological Reports, 59(3).
https://hdl.handle.net/21.15107/rcub_ibiss_1605

Oreščanin Dušić Z, Milovanović SR, Spasić SD, Jones DR, Spasić M. Different responses of mesenteric artery from normotensive and spontaneously hypertensive rats to nitric oxide and its redox congeners. in Pharmacological Reports. 2007;59(3):null-322.
https://hdl.handle.net/21.15107/rcub_ibiss_1605 .

Oreščanin Dušić, Zorana, Milovanović, Slobodan R, Spasić, Snezana D, Jones, David R, Spasić, Mihajlo, "Different responses of mesenteric artery from normotensive and spontaneously hypertensive rats to nitric oxide and its redox congeners" in Pharmacological Reports, 59, no. 3 (2007),
https://hdl.handle.net/21.15107/rcub_ibiss_1605 .

TY  - JOUR
AU  - Marković, Snezana D
AU  - Vukajlović, Miroslava Đ
AU  - Ognjanović, Branka I
AU  - Stajn, Andras S
AU  - Žikić, Radoslav V.
AU  - Saičić, Zorica
AU  - Radojičić, Ratko M.
AU  - Jones, David R
AU  - Spasić, Mihajlo
PY  - 2007
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1602
AB  - After enzymic biotransformation, molsidomine (MO) acts via the metabolite 3-morpholmosydnonimine (SIN-1) through spontaneous liberation of nitric oxide (NO) and superoxide (O-2(.-)). The aim of this study was to compare the effects of MO and its active metabolite SIN-1 on the redox status of rat erythrocytes and reticulocytes. Rat erythrocyte as well as reticulocyte-rich red blood cell (RBC) suspensions were aerobically incubated (2h, 37 degrees C) without (control) or in the presence of different concentrations of MO or SIN-1. In rat erythrocytes, biotransformation of MO resulted in the production of NO and nitroxyl (NO-). Endogenous superoxide anion (O-2(.-)) participated in peroxynitrite generation. SIN-1 simultaneously liberated NO and O-2(.-), which formed peroxynitrite (at least in part), but the liberated NO predominantly reacted with haemoglobin, forming methaemoglobin in erythrocytes. In reticulocytes, MO and SIN-1 caused an increase in the levels of both nitrite and 3-nitrotyrosine (an indicator of peroxynitrite), whereas they decreased the level of O-2(.-). In reticulocytes, MO was metabolized into SIN-1 which led to the generation of NO, which reacted with O-2(.-) (endogenous or exogenous) forming reactive nitrogen species. In conclusion, there are two metabolic pathways for MO biotransformation: one causing NO and NO- generation predominantly in erythrocytes and the other, via SINA metabolism, in reticulocytes. The main difference between the action of MO and SIN-1 was that the latter caused oxidative damage in RBCs. Copyright (c) 2006 John Wiley & Sons, Ltd.
T2  - Cell Biochemistry and Function
T1  - A comparative study of the effects of molsidomine and 3-morpholinosydnonimine on the redox status of rat erythrocytes and reticulocytes
IS  - 3
VL  - 25
EP  - 258
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1602
ER  - 

@article{
author = "Marković, Snezana D and Vukajlović, Miroslava Đ and Ognjanović, Branka I and Stajn, Andras S and Žikić, Radoslav V. and Saičić, Zorica and Radojičić, Ratko M. and Jones, David R and Spasić, Mihajlo",
year = "2007",
abstract = "After enzymic biotransformation, molsidomine (MO) acts via the metabolite 3-morpholmosydnonimine (SIN-1) through spontaneous liberation of nitric oxide (NO) and superoxide (O-2(.-)). The aim of this study was to compare the effects of MO and its active metabolite SIN-1 on the redox status of rat erythrocytes and reticulocytes. Rat erythrocyte as well as reticulocyte-rich red blood cell (RBC) suspensions were aerobically incubated (2h, 37 degrees C) without (control) or in the presence of different concentrations of MO or SIN-1. In rat erythrocytes, biotransformation of MO resulted in the production of NO and nitroxyl (NO-). Endogenous superoxide anion (O-2(.-)) participated in peroxynitrite generation. SIN-1 simultaneously liberated NO and O-2(.-), which formed peroxynitrite (at least in part), but the liberated NO predominantly reacted with haemoglobin, forming methaemoglobin in erythrocytes. In reticulocytes, MO and SIN-1 caused an increase in the levels of both nitrite and 3-nitrotyrosine (an indicator of peroxynitrite), whereas they decreased the level of O-2(.-). In reticulocytes, MO was metabolized into SIN-1 which led to the generation of NO, which reacted with O-2(.-) (endogenous or exogenous) forming reactive nitrogen species. In conclusion, there are two metabolic pathways for MO biotransformation: one causing NO and NO- generation predominantly in erythrocytes and the other, via SINA metabolism, in reticulocytes. The main difference between the action of MO and SIN-1 was that the latter caused oxidative damage in RBCs. Copyright (c) 2006 John Wiley & Sons, Ltd.",
journal = "Cell Biochemistry and Function",
title = "A comparative study of the effects of molsidomine and 3-morpholinosydnonimine on the redox status of rat erythrocytes and reticulocytes",
number = "3",
volume = "25",
pages = "258",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1602"
}

Marković, S. D., Vukajlović, M. Đ., Ognjanović, B. I., Stajn, A. S., Žikić, R. V., Saičić, Z., Radojičić, R. M., Jones, D. R.,& Spasić, M.. (2007). A comparative study of the effects of molsidomine and 3-morpholinosydnonimine on the redox status of rat erythrocytes and reticulocytes. in Cell Biochemistry and Function, 25(3).
https://hdl.handle.net/21.15107/rcub_ibiss_1602

Marković SD, Vukajlović MĐ, Ognjanović BI, Stajn AS, Žikić RV, Saičić Z, Radojičić RM, Jones DR, Spasić M. A comparative study of the effects of molsidomine and 3-morpholinosydnonimine on the redox status of rat erythrocytes and reticulocytes. in Cell Biochemistry and Function. 2007;25(3):null-258.
https://hdl.handle.net/21.15107/rcub_ibiss_1602 .

Marković, Snezana D, Vukajlović, Miroslava Đ, Ognjanović, Branka I, Stajn, Andras S, Žikić, Radoslav V., Saičić, Zorica, Radojičić, Ratko M., Jones, David R, Spasić, Mihajlo, "A comparative study of the effects of molsidomine and 3-morpholinosydnonimine on the redox status of rat erythrocytes and reticulocytes" in Cell Biochemistry and Function, 25, no. 3 (2007),
https://hdl.handle.net/21.15107/rcub_ibiss_1602 .

TY  - JOUR
AU  - Adžić, Miroslav
AU  - Niciforović, Ana
AU  - Vucić, Vesna
AU  - Nešković-Konstantinović, Zora B.
AU  - Spasić, Snezana D
AU  - Jones, David R
AU  - Radojcić, Marija B
AU  - Spasić, Mihajlo
PY  - 2006
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1655
AB  - There is a well-established role for reactive oxygen and nitrogen species, chronic inflammation and immune response in the pathogenesis of breast cancer. Complex interactions between breast cancer cells and surrounding blood vessels are prerequisites for cancer growth and invasion. Reports in the literature concerning the systemic response to, and the effect of, common breast cancer therapy on NF-kappa B and antioxidative defence enzyme expression and activity under clinical conditions are scarce. We determined these parameters in whole blood cell lysate from 16 women with breast cancer before and after combined (cyclophosphamide, doxorubicin, 5-fluorouracil; CAF) therapy and compared the results with 16 healthy women. Significantly higher levels of NF-kappa B and Mn-SOD (both their protein level and their activity) were found in breast cancer patients before and after CAF therapy, in comparison with healthy women. In parallel measurements, no change in the level or activity of catalase (CAT) was detected. According to our findings, it appears that breast cancer creates conditions that increase the level of hydrogen peroxide in the circulating cells and that the applied CAF therapy fails to compensate, therefore creating systemic conditions that favour survival and invasion of breast cancer cells.
T2  - Redox Report
T1  - Systemic NF-kappa B activation in blood cells of breast cancer patients
IS  - 1
VL  - 11
EP  - 44
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1655
ER  - 

@article{
author = "Adžić, Miroslav and Niciforović, Ana and Vucić, Vesna and Nešković-Konstantinović, Zora B. and Spasić, Snezana D and Jones, David R and Radojcić, Marija B and Spasić, Mihajlo",
year = "2006",
abstract = "There is a well-established role for reactive oxygen and nitrogen species, chronic inflammation and immune response in the pathogenesis of breast cancer. Complex interactions between breast cancer cells and surrounding blood vessels are prerequisites for cancer growth and invasion. Reports in the literature concerning the systemic response to, and the effect of, common breast cancer therapy on NF-kappa B and antioxidative defence enzyme expression and activity under clinical conditions are scarce. We determined these parameters in whole blood cell lysate from 16 women with breast cancer before and after combined (cyclophosphamide, doxorubicin, 5-fluorouracil; CAF) therapy and compared the results with 16 healthy women. Significantly higher levels of NF-kappa B and Mn-SOD (both their protein level and their activity) were found in breast cancer patients before and after CAF therapy, in comparison with healthy women. In parallel measurements, no change in the level or activity of catalase (CAT) was detected. According to our findings, it appears that breast cancer creates conditions that increase the level of hydrogen peroxide in the circulating cells and that the applied CAF therapy fails to compensate, therefore creating systemic conditions that favour survival and invasion of breast cancer cells.",
journal = "Redox Report",
title = "Systemic NF-kappa B activation in blood cells of breast cancer patients",
number = "1",
volume = "11",
pages = "44",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1655"
}

Adžić, M., Niciforović, A., Vucić, V., Nešković-Konstantinović, Z. B., Spasić, S. D., Jones, D. R., Radojcić, M. B.,& Spasić, M.. (2006). Systemic NF-kappa B activation in blood cells of breast cancer patients. in Redox Report, 11(1).
https://hdl.handle.net/21.15107/rcub_ibiss_1655

Adžić M, Niciforović A, Vucić V, Nešković-Konstantinović ZB, Spasić SD, Jones DR, Radojcić MB, Spasić M. Systemic NF-kappa B activation in blood cells of breast cancer patients. in Redox Report. 2006;11(1):null-44.
https://hdl.handle.net/21.15107/rcub_ibiss_1655 .

Adžić, Miroslav, Niciforović, Ana, Vucić, Vesna, Nešković-Konstantinović, Zora B., Spasić, Snezana D, Jones, David R, Radojcić, Marija B, Spasić, Mihajlo, "Systemic NF-kappa B activation in blood cells of breast cancer patients" in Redox Report, 11, no. 1 (2006),
https://hdl.handle.net/21.15107/rcub_ibiss_1655 .

TY  - JOUR
AU  - Nikolić-Kokić, Aleksandra
AU  - Stević, Zorica D
AU  - Blagojević, Duško
AU  - Davidović, Biljana
AU  - Jones, David R
AU  - Spasić, Mihajlo
PY  - 2006
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1647
AB  - Background: Overproduction of nitric oxide (NO) and hydrogen peroxide (H2O2) may be an important factor in the pathogenesis of amyotrophic lateral sclerosis (ALS). Owing to their ability to permeate through biological membranes, excess NO and H2O2 may be present in the media surrounding motor neurones. Anti-oxidative defence enzymes (ADEs) in erythrocytes are capable of detoxifying reactive oxygen species (produced endogenously or exogenously), but may also be structurally modified and inactivated by reactive oxygen and nitrogen species. Both balanced and coordinated ADE activities are of utmost importance for their correct physiological function. Methods: We determined activity of the following ADEs: copper-zinc superoxide dismutase (CuZn SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) in erythrocytes from sporadic ALS patients [SALS (-/+)], familial ALS patients with the Leu144Phe mutation in the SOD1 gene [FALS (+/-)], asymptomatic carriers with the Leu144Phe mutation in the SOD1 gene (+/-), and control subjects (-/-). We also examined the in vitro effect of diethyldithiocarbamate (DDC) on CuZn SOD activity in erythrocytes from FALS patients, SALS patients and control subjects. Results: The influence of the Leu144Phe mutation and/or disease was apparent for ADE activities measured in all three patient groups. The SOD1 gene mutation decreased CuZn SOD and GSH-Px activity (two-way ANOVA, significant mutation effect). We noted that the disease also contributed to decreased CuZn SOD activity in SALS patients in comparison with the control group (two-way ANOVA, mutation and disease effect). The disease also influenced CAT and GR activity. CAT activity was decreased in both SALS and FALS patients. In all three patient groups, GR activity was higher than in the control group. Finally, DDC inhibited CuZn SOD activity in erythrocytes from control subjects, FALS (Leu144Phe) patients and SALS patients; however, its effect was more pronounced and significant in FALS patients. Conclusions: Changes in erythrocyte ADE activities suggest that oxidative stress, involved in the motor neurone pathogenesis of SALS and FALS, also has systemic effects. Differences in ADE systems between the study groups revealed the presence of different types of oxidative pressure, indicating the potential additional benefit of individually designed anti-oxidant cocktail therapies.
T2  - Clinical Chemistry and Laboratory Medicine
T1  - Alterations in anti-oxidative defence enzymes in erythrocytes from sporadic amyotrophic lateral sclerosis (SALS) and familial ALS patients
IS  - 5
VL  - 44
EP  - 593
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1647
ER  - 

@article{
author = "Nikolić-Kokić, Aleksandra and Stević, Zorica D and Blagojević, Duško and Davidović, Biljana and Jones, David R and Spasić, Mihajlo",
year = "2006",
abstract = "Background: Overproduction of nitric oxide (NO) and hydrogen peroxide (H2O2) may be an important factor in the pathogenesis of amyotrophic lateral sclerosis (ALS). Owing to their ability to permeate through biological membranes, excess NO and H2O2 may be present in the media surrounding motor neurones. Anti-oxidative defence enzymes (ADEs) in erythrocytes are capable of detoxifying reactive oxygen species (produced endogenously or exogenously), but may also be structurally modified and inactivated by reactive oxygen and nitrogen species. Both balanced and coordinated ADE activities are of utmost importance for their correct physiological function. Methods: We determined activity of the following ADEs: copper-zinc superoxide dismutase (CuZn SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) in erythrocytes from sporadic ALS patients [SALS (-/+)], familial ALS patients with the Leu144Phe mutation in the SOD1 gene [FALS (+/-)], asymptomatic carriers with the Leu144Phe mutation in the SOD1 gene (+/-), and control subjects (-/-). We also examined the in vitro effect of diethyldithiocarbamate (DDC) on CuZn SOD activity in erythrocytes from FALS patients, SALS patients and control subjects. Results: The influence of the Leu144Phe mutation and/or disease was apparent for ADE activities measured in all three patient groups. The SOD1 gene mutation decreased CuZn SOD and GSH-Px activity (two-way ANOVA, significant mutation effect). We noted that the disease also contributed to decreased CuZn SOD activity in SALS patients in comparison with the control group (two-way ANOVA, mutation and disease effect). The disease also influenced CAT and GR activity. CAT activity was decreased in both SALS and FALS patients. In all three patient groups, GR activity was higher than in the control group. Finally, DDC inhibited CuZn SOD activity in erythrocytes from control subjects, FALS (Leu144Phe) patients and SALS patients; however, its effect was more pronounced and significant in FALS patients. Conclusions: Changes in erythrocyte ADE activities suggest that oxidative stress, involved in the motor neurone pathogenesis of SALS and FALS, also has systemic effects. Differences in ADE systems between the study groups revealed the presence of different types of oxidative pressure, indicating the potential additional benefit of individually designed anti-oxidant cocktail therapies.",
journal = "Clinical Chemistry and Laboratory Medicine",
title = "Alterations in anti-oxidative defence enzymes in erythrocytes from sporadic amyotrophic lateral sclerosis (SALS) and familial ALS patients",
number = "5",
volume = "44",
pages = "593",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1647"
}

Nikolić-Kokić, A., Stević, Z. D., Blagojević, D., Davidović, B., Jones, D. R.,& Spasić, M.. (2006). Alterations in anti-oxidative defence enzymes in erythrocytes from sporadic amyotrophic lateral sclerosis (SALS) and familial ALS patients. in Clinical Chemistry and Laboratory Medicine, 44(5).
https://hdl.handle.net/21.15107/rcub_ibiss_1647

Nikolić-Kokić A, Stević ZD, Blagojević D, Davidović B, Jones DR, Spasić M. Alterations in anti-oxidative defence enzymes in erythrocytes from sporadic amyotrophic lateral sclerosis (SALS) and familial ALS patients. in Clinical Chemistry and Laboratory Medicine. 2006;44(5):null-593.
https://hdl.handle.net/21.15107/rcub_ibiss_1647 .

Nikolić-Kokić, Aleksandra, Stević, Zorica D, Blagojević, Duško, Davidović, Biljana, Jones, David R, Spasić, Mihajlo, "Alterations in anti-oxidative defence enzymes in erythrocytes from sporadic amyotrophic lateral sclerosis (SALS) and familial ALS patients" in Clinical Chemistry and Laboratory Medicine, 44, no. 5 (2006),
https://hdl.handle.net/21.15107/rcub_ibiss_1647 .

TY  - JOUR
AU  - Nikolić-Kokić, Aleksandra
AU  - Stević, Zorica D
AU  - Stojanović, Srđan D.
AU  - Blagojević, Duško
AU  - Jones, David R
AU  - Pavlović, Sanja
AU  - Niketić, Vesna P
AU  - Apostolski, Slobodan A
AU  - Spasić, Mihajlo
PY  - 2005
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1689
AB  - Recent findings indicate that nitric oxide (NOcenter dot) over-production might be an important factor in the pathogenesis of sporadic amyotrophic lateral sclerosis (SALS). We measured significantly higher concentrations of uric acid and thiol group-containing molecules (R-SH groups) in the cerebrospinal fluid (CSF) from SALS patients compared to controls. The above factors, together with a slightly increased free iron concentration found in the CSF, favour conditions necessary for the formation of the dinitrosyl iron complex, capable of NOcenter dot bio-transformation. Thus, we performed ex vivo saturation of CSF ( from both SALS patients and controls) with NOcenter dot. A decrease in the level of R - SH was found. This was more pronounced in the CSF from SALS patients. In the CSF from SALS patients the production of nitrite and hydroxylamine was greater than that observed in the CSF from controls. Moreover, we also found increased Cu, Zn-SOD activity in the CSF from SALS patients ( when compared to control subjects) but no activity corresponding to Mn-SOD in any CSF samples. As Cu, Zn-SOD can react with nitroxyl forming NOcenter dot, the conditions for a closed, but continuous, loop of NOcenter dot biotransformation are present in the CSF of ALS patients.
T2  - Redox Report
T1  - Biotransformation of nitric oxide in the cerebrospinal fluid of amyotrophic lateral sclerosis patients
IS  - 5
VL  - 10
EP  - 270
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1689
ER  - 

@article{
author = "Nikolić-Kokić, Aleksandra and Stević, Zorica D and Stojanović, Srđan D. and Blagojević, Duško and Jones, David R and Pavlović, Sanja and Niketić, Vesna P and Apostolski, Slobodan A and Spasić, Mihajlo",
year = "2005",
abstract = "Recent findings indicate that nitric oxide (NOcenter dot) over-production might be an important factor in the pathogenesis of sporadic amyotrophic lateral sclerosis (SALS). We measured significantly higher concentrations of uric acid and thiol group-containing molecules (R-SH groups) in the cerebrospinal fluid (CSF) from SALS patients compared to controls. The above factors, together with a slightly increased free iron concentration found in the CSF, favour conditions necessary for the formation of the dinitrosyl iron complex, capable of NOcenter dot bio-transformation. Thus, we performed ex vivo saturation of CSF ( from both SALS patients and controls) with NOcenter dot. A decrease in the level of R - SH was found. This was more pronounced in the CSF from SALS patients. In the CSF from SALS patients the production of nitrite and hydroxylamine was greater than that observed in the CSF from controls. Moreover, we also found increased Cu, Zn-SOD activity in the CSF from SALS patients ( when compared to control subjects) but no activity corresponding to Mn-SOD in any CSF samples. As Cu, Zn-SOD can react with nitroxyl forming NOcenter dot, the conditions for a closed, but continuous, loop of NOcenter dot biotransformation are present in the CSF of ALS patients.",
journal = "Redox Report",
title = "Biotransformation of nitric oxide in the cerebrospinal fluid of amyotrophic lateral sclerosis patients",
number = "5",
volume = "10",
pages = "270",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1689"
}

Nikolić-Kokić, A., Stević, Z. D., Stojanović, S. D., Blagojević, D., Jones, D. R., Pavlović, S., Niketić, V. P., Apostolski, S. A.,& Spasić, M.. (2005). Biotransformation of nitric oxide in the cerebrospinal fluid of amyotrophic lateral sclerosis patients. in Redox Report, 10(5).
https://hdl.handle.net/21.15107/rcub_ibiss_1689

Nikolić-Kokić A, Stević ZD, Stojanović SD, Blagojević D, Jones DR, Pavlović S, Niketić VP, Apostolski SA, Spasić M. Biotransformation of nitric oxide in the cerebrospinal fluid of amyotrophic lateral sclerosis patients. in Redox Report. 2005;10(5):null-270.
https://hdl.handle.net/21.15107/rcub_ibiss_1689 .

Nikolić-Kokić, Aleksandra, Stević, Zorica D, Stojanović, Srđan D., Blagojević, Duško, Jones, David R, Pavlović, Sanja, Niketić, Vesna P, Apostolski, Slobodan A, Spasić, Mihajlo, "Biotransformation of nitric oxide in the cerebrospinal fluid of amyotrophic lateral sclerosis patients" in Redox Report, 10, no. 5 (2005),
https://hdl.handle.net/21.15107/rcub_ibiss_1689 .