TY  - JOUR
AU  - Mijevic, Cedo
AU  - Nikolić, Milan
AU  - Nikolić-Kokić, Aleksandra
AU  - Jones, David R.
AU  - Niketić, Vesna
AU  - Lecic-Tosevski, Dusica
AU  - Spasić, Mihajlo B.
PY  - 2010
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1059
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 lt 0.01) and total cholesterol and phospholipids (by 8% and 11%, respectively p lt 0.05) in patients were found. CuZn-superoxide dismutase (SOD1) activity was markedly higher (by 35%, p lt 0.001) while selenium-dependent glutathione peroxidase (GSH-Px1) activity was markedly lower (by 41%, p lt 0.001) in patients. In addition, metHb and HbA1c levels in patients were significantly higher (by 58% and 25%. respectively p lt 0.001). SOD1 activity was negatively correlated (p lt 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.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Progress in Neuro-psychopharmacology and Biological Psychiatry
T1  - Lipid status, anti-oxidant enzyme defence and haemoglobin content in the blood of long-term clozapine-treated schizophrenic patients
VL  - 34
IS  - 2
SP  - 303
EP  - 307
DO  - 10.1016/j.pnpbp.2009.11.024
ER  - 

@article{
author = "Mijevic, Cedo and Nikolić, Milan and Nikolić-Kokić, Aleksandra and Jones, David R. and Niketić, Vesna and Lecic-Tosevski, Dusica and Spasić, Mihajlo B.",
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 lt 0.01) and total cholesterol and phospholipids (by 8% and 11%, respectively p lt 0.05) in patients were found. CuZn-superoxide dismutase (SOD1) activity was markedly higher (by 35%, p lt 0.001) while selenium-dependent glutathione peroxidase (GSH-Px1) activity was markedly lower (by 41%, p lt 0.001) in patients. In addition, metHb and HbA1c levels in patients were significantly higher (by 58% and 25%. respectively p lt 0.001). SOD1 activity was negatively correlated (p lt 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.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Progress in Neuro-psychopharmacology and Biological Psychiatry",
title = "Lipid status, anti-oxidant enzyme defence and haemoglobin content in the blood of long-term clozapine-treated schizophrenic patients",
volume = "34",
number = "2",
pages = "303-307",
doi = "10.1016/j.pnpbp.2009.11.024"
}

Mijevic, C., Nikolić, M., Nikolić-Kokić, A., Jones, D. R., Niketić, V., Lecic-Tosevski, D.,& Spasić, M. B.. (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 and Biological Psychiatry
Pergamon-Elsevier Science Ltd, Oxford., 34(2), 303-307.
https://doi.org/10.1016/j.pnpbp.2009.11.024

Mijevic C, Nikolić M, Nikolić-Kokić A, Jones DR, Niketić V, Lecic-Tosevski D, Spasić MB. Lipid status, anti-oxidant enzyme defence and haemoglobin content in the blood of long-term clozapine-treated schizophrenic patients. in Progress in Neuro-psychopharmacology and Biological Psychiatry. 2010;34(2):303-307.
doi:10.1016/j.pnpbp.2009.11.024 .

Mijevic, Cedo, Nikolić, Milan, Nikolić-Kokić, Aleksandra, Jones, David R., Niketić, Vesna, Lecic-Tosevski, Dusica, Spasić, Mihajlo B., "Lipid status, anti-oxidant enzyme defence and haemoglobin content in the blood of long-term clozapine-treated schizophrenic patients" in Progress in Neuro-psychopharmacology and Biological Psychiatry, 34, no. 2 (2010):303-307,
https://doi.org/10.1016/j.pnpbp.2009.11.024 . .

TY  - JOUR
AU  - Nikolić, Milan
AU  - Nikolić-Kokić, Aleksandra
AU  - Stanić, Dragana
AU  - Blagojević, Duško P.
AU  - Vranić, Danijela
AU  - Jones, David R.
AU  - Niketić, Vesna
AU  - Spasić, Mihajlo B.
PY  - 2007
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/837
AB  - In a previous study, it was shown that the lipid fraction, which is occasionally observed in red blood cell hemolysates, represents cholesterol (Ch) associated with phospholipid firmly bound to haemoglobin (termed Hb-Ch). The current study was conducted to investigate whether Hb-Ch could affect the primary anti-oxidant enzyme defence system in human erythrocytes. Sixty healthy volunteers were used for the current study. Group 1 consisted of 28 subjects without or with a low level of Hb-Ch. Group 2 comprised 32 subjects with a considerably higher level of Hb-Ch. The activities of erythrocyte superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, as well as the content of methaemoglobin (metHb) were measured in both groups. The results indicated that the amount of Hb-Ch neither influenced the activities of the erythrocyte anti-oxidant enzymes nor altered the level of metHb. However, a higher amount of Hb-Ch changed the correlations in the part of the anti-oxidant defence system relating to glutathione, suggesting increased peroxidative pressure from plasma lipids. Group 2 also had significantly increased concentrations of total plasma Ch and triglycerides. Together, these facts are strong indications that the anti-oxidant defence system in human erythrocytes finely retunes its composition according to plasma oxidative demands.
AB  - U prethodnom radu pokazano je da lipidna frakcija koja se javlja u hemolizatu zdravih ljudi predstavlja holesterol (asosovan sa fosfolipidima) čvrsto vezan za hemoglobin (Hb-Ch). U ovom radu ispitivan je uticaj Hb-Ch na anti-oksidativni enzimski sistem u humanim eritrocitima. Određena je aktivnost superoksid-dizmutaze, katalaze, glutation-peroksidaze i glutation-reduktaze, kao i sadržaj met-hemoglobina (metHb) u eritrocitima 60 ljudi, podeljenih u dve grupe na osnovu količine Hb-Ch. Rezultati pokazuju da količina prisutnog Hb-Ch ne menja aktivnost merenih enzima, niti nivo metHb. Međutim, u grupi ispitanika sa povećanim sadržajem Hb-Ch zapažene su korelativne promene u delu anti-oksidativnog enzimskog sistema povezanog sa glutationom. U istoj grupi detektovane su i veće koncentracije ukupnog holesterola i triglicerida u plazmi, što zajedno ukazuje na povećani peroksidativni pritisak iz plazme. Ovi rezultati ukazuju da odbrambeni anti-oksidativni enzimski sistem u humanim eritrocitima prilagođava svoju organizaciju prema zahtevima iz svog okruženja. .
PB  - Serbian Chemical Soc, Belgrade
T2  - Journal of the Serbian Chemical Society
T1  - Does cholesterol bound to haemoglobin affect the anti-oxidant enzyme defence system in human erythrocytes?
T1  - Da li holesterol vezan za hemoglobin utiče na anti-oksidativni enzimski sistem u humanim eritrocitima?
VL  - 72
IS  - 4
SP  - 339
EP  - 345
DO  - 10.2298/JSC0704339N
ER  - 

@article{
author = "Nikolić, Milan and Nikolić-Kokić, Aleksandra and Stanić, Dragana and Blagojević, Duško P. and Vranić, Danijela and Jones, David R. and Niketić, Vesna and Spasić, Mihajlo B.",
year = "2007",
abstract = "In a previous study, it was shown that the lipid fraction, which is occasionally observed in red blood cell hemolysates, represents cholesterol (Ch) associated with phospholipid firmly bound to haemoglobin (termed Hb-Ch). The current study was conducted to investigate whether Hb-Ch could affect the primary anti-oxidant enzyme defence system in human erythrocytes. Sixty healthy volunteers were used for the current study. Group 1 consisted of 28 subjects without or with a low level of Hb-Ch. Group 2 comprised 32 subjects with a considerably higher level of Hb-Ch. The activities of erythrocyte superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, as well as the content of methaemoglobin (metHb) were measured in both groups. The results indicated that the amount of Hb-Ch neither influenced the activities of the erythrocyte anti-oxidant enzymes nor altered the level of metHb. However, a higher amount of Hb-Ch changed the correlations in the part of the anti-oxidant defence system relating to glutathione, suggesting increased peroxidative pressure from plasma lipids. Group 2 also had significantly increased concentrations of total plasma Ch and triglycerides. Together, these facts are strong indications that the anti-oxidant defence system in human erythrocytes finely retunes its composition according to plasma oxidative demands., U prethodnom radu pokazano je da lipidna frakcija koja se javlja u hemolizatu zdravih ljudi predstavlja holesterol (asosovan sa fosfolipidima) čvrsto vezan za hemoglobin (Hb-Ch). U ovom radu ispitivan je uticaj Hb-Ch na anti-oksidativni enzimski sistem u humanim eritrocitima. Određena je aktivnost superoksid-dizmutaze, katalaze, glutation-peroksidaze i glutation-reduktaze, kao i sadržaj met-hemoglobina (metHb) u eritrocitima 60 ljudi, podeljenih u dve grupe na osnovu količine Hb-Ch. Rezultati pokazuju da količina prisutnog Hb-Ch ne menja aktivnost merenih enzima, niti nivo metHb. Međutim, u grupi ispitanika sa povećanim sadržajem Hb-Ch zapažene su korelativne promene u delu anti-oksidativnog enzimskog sistema povezanog sa glutationom. U istoj grupi detektovane su i veće koncentracije ukupnog holesterola i triglicerida u plazmi, što zajedno ukazuje na povećani peroksidativni pritisak iz plazme. Ovi rezultati ukazuju da odbrambeni anti-oksidativni enzimski sistem u humanim eritrocitima prilagođava svoju organizaciju prema zahtevima iz svog okruženja. .",
publisher = "Serbian Chemical Soc, Belgrade",
journal = "Journal of the Serbian Chemical Society",
title = "Does cholesterol bound to haemoglobin affect the anti-oxidant enzyme defence system in human erythrocytes?, Da li holesterol vezan za hemoglobin utiče na anti-oksidativni enzimski sistem u humanim eritrocitima?",
volume = "72",
number = "4",
pages = "339-345",
doi = "10.2298/JSC0704339N"
}

Nikolić, M., Nikolić-Kokić, A., Stanić, D., Blagojević, D. P., Vranić, D., Jones, D. R., Niketić, V.,& Spasić, M. B.. (2007). Does cholesterol bound to haemoglobin affect the anti-oxidant enzyme defence system in human erythrocytes?. in Journal of the Serbian Chemical Society
Serbian Chemical Soc, Belgrade., 72(4), 339-345.
https://doi.org/10.2298/JSC0704339N

Nikolić M, Nikolić-Kokić A, Stanić D, Blagojević DP, Vranić D, Jones DR, Niketić V, Spasić MB. Does cholesterol bound to haemoglobin affect the anti-oxidant enzyme defence system in human erythrocytes?. in Journal of the Serbian Chemical Society. 2007;72(4):339-345.
doi:10.2298/JSC0704339N .

Nikolić, Milan, Nikolić-Kokić, Aleksandra, Stanić, Dragana, Blagojević, Duško P., Vranić, Danijela, Jones, David R., Niketić, Vesna, Spasić, Mihajlo B., "Does cholesterol bound to haemoglobin affect the anti-oxidant enzyme defence system in human erythrocytes?" in Journal of the Serbian Chemical Society, 72, no. 4 (2007):339-345,
https://doi.org/10.2298/JSC0704339N . .

TY  - JOUR
AU  - Nikolić, Milan
AU  - Stanić, Dragana
AU  - Barievic, Ivona
AU  - Jones, David R.
AU  - Nedić, Olgica
AU  - Niketić, Vesna
PY  - 2007
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/824
AB  - Objective: The interior of red blood cells (RBCs) contains a variable amount of cholesterol and phospholipids bound to haemoglobin (Hb). This current study was devised to determine if this pool of lipids (termed Hb-Ch) was available for exchange with plasma lipoproteins. Design and methods: We studied the in vitro efflux of lipids from human RBCs into fasting plasma in men with either low (control group) or high Hb-Ch (study group). Results: When plasma was incubated with a two-fold excess of autologous RBCs the plasma cholesterol level increased due to a decrease in the level of cholesterol from the RBC membrane (in the control group) and due to a decrease in the level of cholesterol both from the RBC membrane and the Hb-Ch fraction (in the study group). The loss of Hb-Ch-derived phospholipids during lipid efflux was roughly equal to that of Hb-Ch-derived cholesterol. The loss of RBC cholesterol into plasma high-density lipoproteins (HDL) was more pronounced in our study group and correlated with the loss of cholesterol from Hb-Ch. Conclusion: The Hb-Ch adduct significantly contributes to the lipid efflux from RBCs into plasma. The majority of cholesterol released from Hb-Ch appears in the plasma HDL fraction suggesting that Hb-Ch may play a role in reverse cholesterol transport in vivo. (c) 2006 Published by The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Clinical Biochemistry
T1  - Efflux of cholesterol and phospholipids derived from the haemoglobin-lipid adduct in human red blood cells into plasma
VL  - 40
IS  - 5-6
SP  - 305
EP  - 309
DO  - 10.1016/j.clinbiochem.2006.11.005
ER  - 

@article{
author = "Nikolić, Milan and Stanić, Dragana and Barievic, Ivona and Jones, David R. and Nedić, Olgica and Niketić, Vesna",
year = "2007",
abstract = "Objective: The interior of red blood cells (RBCs) contains a variable amount of cholesterol and phospholipids bound to haemoglobin (Hb). This current study was devised to determine if this pool of lipids (termed Hb-Ch) was available for exchange with plasma lipoproteins. Design and methods: We studied the in vitro efflux of lipids from human RBCs into fasting plasma in men with either low (control group) or high Hb-Ch (study group). Results: When plasma was incubated with a two-fold excess of autologous RBCs the plasma cholesterol level increased due to a decrease in the level of cholesterol from the RBC membrane (in the control group) and due to a decrease in the level of cholesterol both from the RBC membrane and the Hb-Ch fraction (in the study group). The loss of Hb-Ch-derived phospholipids during lipid efflux was roughly equal to that of Hb-Ch-derived cholesterol. The loss of RBC cholesterol into plasma high-density lipoproteins (HDL) was more pronounced in our study group and correlated with the loss of cholesterol from Hb-Ch. Conclusion: The Hb-Ch adduct significantly contributes to the lipid efflux from RBCs into plasma. The majority of cholesterol released from Hb-Ch appears in the plasma HDL fraction suggesting that Hb-Ch may play a role in reverse cholesterol transport in vivo. (c) 2006 Published by The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Clinical Biochemistry",
title = "Efflux of cholesterol and phospholipids derived from the haemoglobin-lipid adduct in human red blood cells into plasma",
volume = "40",
number = "5-6",
pages = "305-309",
doi = "10.1016/j.clinbiochem.2006.11.005"
}

Nikolić, M., Stanić, D., Barievic, I., Jones, D. R., Nedić, O.,& Niketić, V.. (2007). Efflux of cholesterol and phospholipids derived from the haemoglobin-lipid adduct in human red blood cells into plasma. in Clinical Biochemistry
Pergamon-Elsevier Science Ltd, Oxford., 40(5-6), 305-309.
https://doi.org/10.1016/j.clinbiochem.2006.11.005

Nikolić M, Stanić D, Barievic I, Jones DR, Nedić O, Niketić V. Efflux of cholesterol and phospholipids derived from the haemoglobin-lipid adduct in human red blood cells into plasma. in Clinical Biochemistry. 2007;40(5-6):305-309.
doi:10.1016/j.clinbiochem.2006.11.005 .

Nikolić, Milan, Stanić, Dragana, Barievic, Ivona, Jones, David R., Nedić, Olgica, Niketić, Vesna, "Efflux of cholesterol and phospholipids derived from the haemoglobin-lipid adduct in human red blood cells into plasma" in Clinical Biochemistry, 40, no. 5-6 (2007):305-309,
https://doi.org/10.1016/j.clinbiochem.2006.11.005 . .

TY  - JOUR
AU  - Nikolić, Milan
AU  - Vranić, Danijela
AU  - Spiric, Aurelija
AU  - Batas, Valentina
AU  - Nikolić-Kokić, Aleksandra
AU  - Radetic, Petar
AU  - Turubatovic, Lazar
AU  - Blagojević, Duško P.
AU  - Jones, David R.
AU  - Niketić, Vesna
AU  - Spasić, Mihajlo B.
PY  - 2006
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/797
AB  - The concept of an anti-oxidant defence system as a means to prevent oxidative cell damage implies balanced activities of anti-oxidant defence enzymes. As well as positive correlations between anti-oxidant enzyme activities in human erythrocytes, it has been observed that sometimes when glutathione peroxidase activity is increased, CuZn-superoxide dismutase activity is decreased. In our current study we have examined the plasma lipid profile and the anti-oxidant defence enzymes in erythrocytes from humans, pigs, and bulls. We found that a negative correlation existed between CuZn-superoxide dismutase and glutathione peroxidase activities in human erythrocytes when the concentrations of both plasma triglycerides and total cholesterol were high. This correlation was also found in pig erythrocytes, but not in bull erythrocytes. We propose that cholesterol could affect membrane lipid peroxiclation and superoxide generation in erythrocytes via the recently found fraction of cholesterol bound to haemoglobin, termed haemoglobin-cholesterol. (c) 2006 Elsevier Inc. All rights reserved.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Biochemical and Biophysical Research Communications
T1  - Could cholesterol bound to haemoglobin be a missing link for the occasional inverse relationship between superoxide dismutase and glutathione peroxidase activities?
VL  - 348
IS  - 1
SP  - 265
EP  - 270
DO  - 10.1016/j.bbrc.2006.06.199
ER  - 

@article{
author = "Nikolić, Milan and Vranić, Danijela and Spiric, Aurelija and Batas, Valentina and Nikolić-Kokić, Aleksandra and Radetic, Petar and Turubatovic, Lazar and Blagojević, Duško P. and Jones, David R. and Niketić, Vesna and Spasić, Mihajlo B.",
year = "2006",
abstract = "The concept of an anti-oxidant defence system as a means to prevent oxidative cell damage implies balanced activities of anti-oxidant defence enzymes. As well as positive correlations between anti-oxidant enzyme activities in human erythrocytes, it has been observed that sometimes when glutathione peroxidase activity is increased, CuZn-superoxide dismutase activity is decreased. In our current study we have examined the plasma lipid profile and the anti-oxidant defence enzymes in erythrocytes from humans, pigs, and bulls. We found that a negative correlation existed between CuZn-superoxide dismutase and glutathione peroxidase activities in human erythrocytes when the concentrations of both plasma triglycerides and total cholesterol were high. This correlation was also found in pig erythrocytes, but not in bull erythrocytes. We propose that cholesterol could affect membrane lipid peroxiclation and superoxide generation in erythrocytes via the recently found fraction of cholesterol bound to haemoglobin, termed haemoglobin-cholesterol. (c) 2006 Elsevier Inc. All rights reserved.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Biochemical and Biophysical Research Communications",
title = "Could cholesterol bound to haemoglobin be a missing link for the occasional inverse relationship between superoxide dismutase and glutathione peroxidase activities?",
volume = "348",
number = "1",
pages = "265-270",
doi = "10.1016/j.bbrc.2006.06.199"
}

Nikolić, M., Vranić, D., Spiric, A., Batas, V., Nikolić-Kokić, A., Radetic, P., Turubatovic, L., Blagojević, D. P., Jones, D. R., Niketić, V.,& Spasić, M. B.. (2006). Could cholesterol bound to haemoglobin be a missing link for the occasional inverse relationship between superoxide dismutase and glutathione peroxidase activities?. in Biochemical and Biophysical Research Communications
Academic Press Inc Elsevier Science, San Diego., 348(1), 265-270.
https://doi.org/10.1016/j.bbrc.2006.06.199

Nikolić M, Vranić D, Spiric A, Batas V, Nikolić-Kokić A, Radetic P, Turubatovic L, Blagojević DP, Jones DR, Niketić V, Spasić MB. Could cholesterol bound to haemoglobin be a missing link for the occasional inverse relationship between superoxide dismutase and glutathione peroxidase activities?. in Biochemical and Biophysical Research Communications. 2006;348(1):265-270.
doi:10.1016/j.bbrc.2006.06.199 .

Nikolić, Milan, Vranić, Danijela, Spiric, Aurelija, Batas, Valentina, Nikolić-Kokić, Aleksandra, Radetic, Petar, Turubatovic, Lazar, Blagojević, Duško P., Jones, David R., Niketić, Vesna, Spasić, Mihajlo B., "Could cholesterol bound to haemoglobin be a missing link for the occasional inverse relationship between superoxide dismutase and glutathione peroxidase activities?" in Biochemical and Biophysical Research Communications, 348, no. 1 (2006):265-270,
https://doi.org/10.1016/j.bbrc.2006.06.199 . .