TY  - JOUR
AU  - Jakovljević, Danijel
AU  - Nikolić, Milan
AU  - Jovanović, Vesna
AU  - Vidonja Uzelac, Teodora
AU  - Nikolić-Kokić, Aleksandra
AU  - Novaković, Emilija
AU  - Miljević, Čedo
AU  - Milovanovć, Maja
AU  - Blagojević, Duško
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6510
AB  - Background: Epilepsy is a chronic brain disease affecting millions of people worldwide,
but little is known about the impact of anti-seizure medications on redox homeostasis. Methods:
This study aimed to compare the effects of the long-term use of oral anti-seizure medications in
monotherapy (lamotrigine, carbamazepine, and valproate) on antioxidant enzymes: superoxide dismutase,
catalase, glutathione peroxidase, glutathione reductase, haemoglobin, and methaemoglobin
content in erythrocytes, and concentrations of total proteins and thiols, nitrites, lipid peroxides and
total glutathione in the plasma of epilepsy patients and drug-naïve patients. Results: The results
showed that lamotrigine therapy led to lower superoxide dismutase activity (p < 0.005) and lower
concentrations of total thiols (p < 0.01) and lipid peroxides (p < 0.01) compared to controls. On the
other hand, therapy with carbamazepine increased nitrite levels (p < 0.01) but reduced superoxide
dismutase activity (p < 0.005). In the valproate group, only a decrease in catalase activity was observed
(p < 0.005). Canonical discriminant analysis showed that the composition of antioxidant enzymes in
erythrocytes was different for both the lamotrigine and carbamazepine groups, while the controls
were separated from all others. Conclusions: Monotherapy with anti-seizure medications discretely
alters redox homeostasis, followed by distinct relationships between antioxidant components.
PB  - Basel: MDPI
T2  - Pharmaceuticals
T1  - Influence of Long-Term Anti-Seizure Medications on Redox Parameters in Human Blood
IS  - 1
VL  - 17
DO  - 10.3390/ph17010130
SP  - 130
ER  - 

@article{
author = "Jakovljević, Danijel and Nikolić, Milan and Jovanović, Vesna and Vidonja Uzelac, Teodora and Nikolić-Kokić, Aleksandra and Novaković, Emilija and Miljević, Čedo and Milovanovć, Maja and Blagojević, Duško",
year = "2024",
abstract = "Background: Epilepsy is a chronic brain disease affecting millions of people worldwide,
but little is known about the impact of anti-seizure medications on redox homeostasis. Methods:
This study aimed to compare the effects of the long-term use of oral anti-seizure medications in
monotherapy (lamotrigine, carbamazepine, and valproate) on antioxidant enzymes: superoxide dismutase,
catalase, glutathione peroxidase, glutathione reductase, haemoglobin, and methaemoglobin
content in erythrocytes, and concentrations of total proteins and thiols, nitrites, lipid peroxides and
total glutathione in the plasma of epilepsy patients and drug-naïve patients. Results: The results
showed that lamotrigine therapy led to lower superoxide dismutase activity (p < 0.005) and lower
concentrations of total thiols (p < 0.01) and lipid peroxides (p < 0.01) compared to controls. On the
other hand, therapy with carbamazepine increased nitrite levels (p < 0.01) but reduced superoxide
dismutase activity (p < 0.005). In the valproate group, only a decrease in catalase activity was observed
(p < 0.005). Canonical discriminant analysis showed that the composition of antioxidant enzymes in
erythrocytes was different for both the lamotrigine and carbamazepine groups, while the controls
were separated from all others. Conclusions: Monotherapy with anti-seizure medications discretely
alters redox homeostasis, followed by distinct relationships between antioxidant components.",
publisher = "Basel: MDPI",
journal = "Pharmaceuticals",
title = "Influence of Long-Term Anti-Seizure Medications on Redox Parameters in Human Blood",
number = "1",
volume = "17",
doi = "10.3390/ph17010130",
pages = "130"
}

Jakovljević, D., Nikolić, M., Jovanović, V., Vidonja Uzelac, T., Nikolić-Kokić, A., Novaković, E., Miljević, Č., Milovanovć, M.,& Blagojević, D.. (2024). Influence of Long-Term Anti-Seizure Medications on Redox Parameters in Human Blood. in Pharmaceuticals
Basel: MDPI., 17(1), 130.
https://doi.org/10.3390/ph17010130

Jakovljević D, Nikolić M, Jovanović V, Vidonja Uzelac T, Nikolić-Kokić A, Novaković E, Miljević Č, Milovanovć M, Blagojević D. Influence of Long-Term Anti-Seizure Medications on Redox Parameters in Human Blood. in Pharmaceuticals. 2024;17(1):130.
doi:10.3390/ph17010130 .

Jakovljević, Danijel, Nikolić, Milan, Jovanović, Vesna, Vidonja Uzelac, Teodora, Nikolić-Kokić, Aleksandra, Novaković, Emilija, Miljević, Čedo, Milovanovć, Maja, Blagojević, Duško, "Influence of Long-Term Anti-Seizure Medications on Redox Parameters in Human Blood" in Pharmaceuticals, 17, no. 1 (2024):130,
https://doi.org/10.3390/ph17010130 . .

TY  - JOUR
AU  - Vukčević, Marija
AU  - Šerović, Katarina
AU  - Despot, Mateja
AU  - Nikolić-Kokić, Aleksandra
AU  - Vujović, Aleksandra
AU  - Nikolić, Milan
AU  - Blagojević, Duško
AU  - Jovanović, Tanja
AU  - Despot, Dragana
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6495
AB  - Background: Several vaccines against COVID-19 have been developed and licensed to
enhance the immune response against SARS-CoV-2. Similarly, previous infection with SARS-CoV-
2 has been shown to provide significant protection against severe infection and hospitalization.
Methods: We investigated the effect of three doses of the Sinopharm vaccine and SARS-CoV-2
infection on the specific immune response in 103 volunteers, measuring neutralizing antibodies, anti-
S1 IgG, anti-RBD IgM, anti-N IgM, anti-N IgG antibodies, and INF γ. Results: Our results showed
that the presence of cardiovascular diseases increased the level of anti-N-IgG antibodies, while
endocrinological diseases decreased the level of neutralizing antibodies and anti-N IgG antibodies,
suggesting that these diseases alter the effect of vaccine-induced immunity. In addition, there was a
significant decrease in anti-S1 IgG levels at 6 months and in anti-N IgG levels 18 months post-infection,
while neutralizing antibodies and INF γ levels were constant at 3, 6, and 18 months post-infection.
Conclusions: Our results confirm the emergence of hybrid immunity, which is the strongest and
most durable compared to natural immunity or vaccine-induced immunity. Significant positive
correlations were found between humoral and cellular immunity markers: neutralizing antibodies,
anti-S1 IgG and anti-N IgG antibodies, and INF γ, indicating a unique coordinated response specific
to COVID-19.
PB  - Basel: MDPI
T2  - Pharmaceuticals
T1  - Humoral and Cellular Immune Response after Three Doses of Sinopharm [Vero Cell]-Inactivated COVID-19 Vaccine in Combination with SARS-CoV-2 Infection Leads to Hybrid Immunity
IS  - 1
VL  - 17
DO  - 10.3390/ph17010122
SP  - 122
ER  - 

@article{
author = "Vukčević, Marija and Šerović, Katarina and Despot, Mateja and Nikolić-Kokić, Aleksandra and Vujović, Aleksandra and Nikolić, Milan and Blagojević, Duško and Jovanović, Tanja and Despot, Dragana",
year = "2024",
abstract = "Background: Several vaccines against COVID-19 have been developed and licensed to
enhance the immune response against SARS-CoV-2. Similarly, previous infection with SARS-CoV-
2 has been shown to provide significant protection against severe infection and hospitalization.
Methods: We investigated the effect of three doses of the Sinopharm vaccine and SARS-CoV-2
infection on the specific immune response in 103 volunteers, measuring neutralizing antibodies, anti-
S1 IgG, anti-RBD IgM, anti-N IgM, anti-N IgG antibodies, and INF γ. Results: Our results showed
that the presence of cardiovascular diseases increased the level of anti-N-IgG antibodies, while
endocrinological diseases decreased the level of neutralizing antibodies and anti-N IgG antibodies,
suggesting that these diseases alter the effect of vaccine-induced immunity. In addition, there was a
significant decrease in anti-S1 IgG levels at 6 months and in anti-N IgG levels 18 months post-infection,
while neutralizing antibodies and INF γ levels were constant at 3, 6, and 18 months post-infection.
Conclusions: Our results confirm the emergence of hybrid immunity, which is the strongest and
most durable compared to natural immunity or vaccine-induced immunity. Significant positive
correlations were found between humoral and cellular immunity markers: neutralizing antibodies,
anti-S1 IgG and anti-N IgG antibodies, and INF γ, indicating a unique coordinated response specific
to COVID-19.",
publisher = "Basel: MDPI",
journal = "Pharmaceuticals",
title = "Humoral and Cellular Immune Response after Three Doses of Sinopharm [Vero Cell]-Inactivated COVID-19 Vaccine in Combination with SARS-CoV-2 Infection Leads to Hybrid Immunity",
number = "1",
volume = "17",
doi = "10.3390/ph17010122",
pages = "122"
}

Vukčević, M., Šerović, K., Despot, M., Nikolić-Kokić, A., Vujović, A., Nikolić, M., Blagojević, D., Jovanović, T.,& Despot, D.. (2024). Humoral and Cellular Immune Response after Three Doses of Sinopharm [Vero Cell]-Inactivated COVID-19 Vaccine in Combination with SARS-CoV-2 Infection Leads to Hybrid Immunity. in Pharmaceuticals
Basel: MDPI., 17(1), 122.
https://doi.org/10.3390/ph17010122

Vukčević M, Šerović K, Despot M, Nikolić-Kokić A, Vujović A, Nikolić M, Blagojević D, Jovanović T, Despot D. Humoral and Cellular Immune Response after Three Doses of Sinopharm [Vero Cell]-Inactivated COVID-19 Vaccine in Combination with SARS-CoV-2 Infection Leads to Hybrid Immunity. in Pharmaceuticals. 2024;17(1):122.
doi:10.3390/ph17010122 .

Vukčević, Marija, Šerović, Katarina, Despot, Mateja, Nikolić-Kokić, Aleksandra, Vujović, Aleksandra, Nikolić, Milan, Blagojević, Duško, Jovanović, Tanja, Despot, Dragana, "Humoral and Cellular Immune Response after Three Doses of Sinopharm [Vero Cell]-Inactivated COVID-19 Vaccine in Combination with SARS-CoV-2 Infection Leads to Hybrid Immunity" in Pharmaceuticals, 17, no. 1 (2024):122,
https://doi.org/10.3390/ph17010122 . .

TY  - JOUR
AU  - Vukčević, Marija
AU  - Nikolić-Kokić, Aleksandra
AU  - Aleksić, Ivan
AU  - Todorović, Sanja
AU  - Oreščanin-Dušić, Zorana
AU  - Blagojević, Duško
AU  - Despot, Dragana
PY  - 2023
UR  - https://academic.oup.com/jee/advance-article/doi/10.1093/jee/toac190/6927190
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5386
AB  - Controlling the number of ticks as carriers of infectious diseases is very important. The process is sometimes compromised by activating the protective mechanisms of the tick itself. Glutathione-S-transferases activity (GSTs) was the subject of our investigation of tick abundance after pyrethroid treatment. We determined GSTs activity in ticks collected from six locations in Belgrade before and after pyrethroid treatment and correlated it with the number of ticks in the locations. The results showed that tick abundance correlated with GSTs activity. On the other hand, treatment efficiency was location-dependent, being similar in each particular location in both April (spring) and October (autumn). Our results suggest that GSTs activity reflects the influence of both present local allelochemicals from different environmental seasonal vegetation and applied pyrethroid. We can conclude that by evaluating GSTs activity in ticks from particular locations as well as during the treatment with acaricides tick removal practice could be improved.
T2  - Journal of Economic Entomology
T1  - Evaluation of Tick Abundance and Pyrethroid Resistance Via Determination of Glutathione-S-Transferases Activity
IS  - 1
VL  - 116
DO  - 10.1093/jee/toac190
SP  - 233
EP  - 239
ER  - 

@article{
author = "Vukčević, Marija and Nikolić-Kokić, Aleksandra and Aleksić, Ivan and Todorović, Sanja and Oreščanin-Dušić, Zorana and Blagojević, Duško and Despot, Dragana",
year = "2023",
abstract = "Controlling the number of ticks as carriers of infectious diseases is very important. The process is sometimes compromised by activating the protective mechanisms of the tick itself. Glutathione-S-transferases activity (GSTs) was the subject of our investigation of tick abundance after pyrethroid treatment. We determined GSTs activity in ticks collected from six locations in Belgrade before and after pyrethroid treatment and correlated it with the number of ticks in the locations. The results showed that tick abundance correlated with GSTs activity. On the other hand, treatment efficiency was location-dependent, being similar in each particular location in both April (spring) and October (autumn). Our results suggest that GSTs activity reflects the influence of both present local allelochemicals from different environmental seasonal vegetation and applied pyrethroid. We can conclude that by evaluating GSTs activity in ticks from particular locations as well as during the treatment with acaricides tick removal practice could be improved.",
journal = "Journal of Economic Entomology",
title = "Evaluation of Tick Abundance and Pyrethroid Resistance Via Determination of Glutathione-S-Transferases Activity",
number = "1",
volume = "116",
doi = "10.1093/jee/toac190",
pages = "233-239"
}

Vukčević, M., Nikolić-Kokić, A., Aleksić, I., Todorović, S., Oreščanin-Dušić, Z., Blagojević, D.,& Despot, D.. (2023). Evaluation of Tick Abundance and Pyrethroid Resistance Via Determination of Glutathione-S-Transferases Activity. in Journal of Economic Entomology, 116(1), 233-239.
https://doi.org/10.1093/jee/toac190

Vukčević M, Nikolić-Kokić A, Aleksić I, Todorović S, Oreščanin-Dušić Z, Blagojević D, Despot D. Evaluation of Tick Abundance and Pyrethroid Resistance Via Determination of Glutathione-S-Transferases Activity. in Journal of Economic Entomology. 2023;116(1):233-239.
doi:10.1093/jee/toac190 .

Vukčević, Marija, Nikolić-Kokić, Aleksandra, Aleksić, Ivan, Todorović, Sanja, Oreščanin-Dušić, Zorana, Blagojević, Duško, Despot, Dragana, "Evaluation of Tick Abundance and Pyrethroid Resistance Via Determination of Glutathione-S-Transferases Activity" in Journal of Economic Entomology, 116, no. 1 (2023):233-239,
https://doi.org/10.1093/jee/toac190 . .

TY  - CONF
AU  - Grahovac, Tanja
AU  - Vidonja Uzelac, Teodora
AU  - Nikolić-Kokić, Aleksandra
AU  - Tatalović, Nikola
AU  - Oreščanin-Dušić, Zorana
AU  - Blagojević, Duško
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5849
AB  - Normal redox status of the cell is maintained by a number of enzymes, such as superoxide dismutase, catalase, glutathione peroxidase and low molecular weight antioxidants. One of the component that determining the redox status of cells is the tripeptide glutathione. Maintaining high levels of reduced glutathione enhances antioxidant defense. The aim of this study was to examine whether, to what extent and in what way changes in physiological processes occurred in conditions when cellular redox homeostasis is in imbalance. The experiments were performed on isolated ileum of male Wistar rats, electrically stimulated and treated with cumulative doses of reduced or oxidized glutathione. The activity of antioxidant enzymes (catalase, glutathione reductase, glutathione peroxidase, copper–zinc superoxide dismutase and manganese superoxide dismutase) was determined in treated ileum.  Glutathione in both forms decreased amplitude of ileum contractions. Cumulative doses of oxidized glutathione led to higher glutathione reductase activity while the addition of reduced glutathione increased activity of glutathione peroxidase. The results showed that maintenance of cellular redox homeostasis have influence to physiological processes.
PB  - Sarajevo: Institute for Genetic Engineering and Biotechnology, University of Sarajevo
C3  - Book of abstracts: International Conference of Biochemists and Molecular Biologists in Bosnia and Herzegovina -ABMBBIH; 2023 May 18-20; Sarajevo, Bosnia and Herzegovina
T1  - Reduced and oxidized glutathione affects smooth muscle contractility and anti-oxidant enzymes activity in isolated ileum of male rat
SP  - 42
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5849
ER  - 

@conference{
author = "Grahovac, Tanja and Vidonja Uzelac, Teodora and Nikolić-Kokić, Aleksandra and Tatalović, Nikola and Oreščanin-Dušić, Zorana and Blagojević, Duško",
year = "2023",
abstract = "Normal redox status of the cell is maintained by a number of enzymes, such as superoxide dismutase, catalase, glutathione peroxidase and low molecular weight antioxidants. One of the component that determining the redox status of cells is the tripeptide glutathione. Maintaining high levels of reduced glutathione enhances antioxidant defense. The aim of this study was to examine whether, to what extent and in what way changes in physiological processes occurred in conditions when cellular redox homeostasis is in imbalance. The experiments were performed on isolated ileum of male Wistar rats, electrically stimulated and treated with cumulative doses of reduced or oxidized glutathione. The activity of antioxidant enzymes (catalase, glutathione reductase, glutathione peroxidase, copper–zinc superoxide dismutase and manganese superoxide dismutase) was determined in treated ileum.  Glutathione in both forms decreased amplitude of ileum contractions. Cumulative doses of oxidized glutathione led to higher glutathione reductase activity while the addition of reduced glutathione increased activity of glutathione peroxidase. The results showed that maintenance of cellular redox homeostasis have influence to physiological processes.",
publisher = "Sarajevo: Institute for Genetic Engineering and Biotechnology, University of Sarajevo",
journal = "Book of abstracts: International Conference of Biochemists and Molecular Biologists in Bosnia and Herzegovina -ABMBBIH; 2023 May 18-20; Sarajevo, Bosnia and Herzegovina",
title = "Reduced and oxidized glutathione affects smooth muscle contractility and anti-oxidant enzymes activity in isolated ileum of male rat",
pages = "42",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5849"
}

Grahovac, T., Vidonja Uzelac, T., Nikolić-Kokić, A., Tatalović, N., Oreščanin-Dušić, Z.,& Blagojević, D.. (2023). Reduced and oxidized glutathione affects smooth muscle contractility and anti-oxidant enzymes activity in isolated ileum of male rat. in Book of abstracts: International Conference of Biochemists and Molecular Biologists in Bosnia and Herzegovina -ABMBBIH; 2023 May 18-20; Sarajevo, Bosnia and Herzegovina
Sarajevo: Institute for Genetic Engineering and Biotechnology, University of Sarajevo., 42.
https://hdl.handle.net/21.15107/rcub_ibiss_5849

Grahovac T, Vidonja Uzelac T, Nikolić-Kokić A, Tatalović N, Oreščanin-Dušić Z, Blagojević D. Reduced and oxidized glutathione affects smooth muscle contractility and anti-oxidant enzymes activity in isolated ileum of male rat. in Book of abstracts: International Conference of Biochemists and Molecular Biologists in Bosnia and Herzegovina -ABMBBIH; 2023 May 18-20; Sarajevo, Bosnia and Herzegovina. 2023;:42.
https://hdl.handle.net/21.15107/rcub_ibiss_5849 .

Grahovac, Tanja, Vidonja Uzelac, Teodora, Nikolić-Kokić, Aleksandra, Tatalović, Nikola, Oreščanin-Dušić, Zorana, Blagojević, Duško, "Reduced and oxidized glutathione affects smooth muscle contractility and anti-oxidant enzymes activity in isolated ileum of male rat" in Book of abstracts: International Conference of Biochemists and Molecular Biologists in Bosnia and Herzegovina -ABMBBIH; 2023 May 18-20; Sarajevo, Bosnia and Herzegovina (2023):42,
https://hdl.handle.net/21.15107/rcub_ibiss_5849 .

TY  - JOUR
AU  - Platanić-Arizanović, Lena
AU  - Gligorijević, Nikola
AU  - Cvijetić, Ilija
AU  - Mijatović, Aleksandar
AU  - Krstić-Ristivojević, Maja
AU  - Minić, Simeon
AU  - Nikolić-Kokić, Aleksandra
AU  - Miljević, Čedo
AU  - Nikolić, Milan
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6028
AB  - : Packed with hemoglobin, an essential protein for oxygen transport, human erythrocytes
are a suitable model system for testing the pleiotropic effects of lipophilic drugs. Our study investigated the interaction between antipsychotic drugs clozapine, ziprasidone, sertindole, and human
hemoglobin under simulated physiological conditions. Analysis of protein fluorescence quenching
at different temperatures and data obtained from the van’t Hoff diagram and molecular docking
indicate that the interactions are static and that the tetrameric human hemoglobin has one binding site
for all drugs in the central cavity near αβ interfaces and is dominantly mediated through hydrophobic
forces. The association constants were lower-moderate strength (~104 M−1
), the highest observed
for clozapine (2.2 × 104 M−1 at 25 ◦C). The clozapine binding showed “friendly” effects: increased
α-helical content, a higher melting point, and protein protection from free radical-mediated oxidation.
On the other hand, bound ziprasidone and sertindole had a slightly pro-oxidative effect, increasing
ferrihemoglobin content, a possible “foe”. Since the interaction of proteins with drugs plays a vital
role in their pharmacokinetic and pharmacodynamic properties, the physiological significance of the
obtained findings is briefly discussed.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?
IS  - 10
VL  - 24
DO  - 10.3390/ijms24108921
SP  - 8921
ER  - 

@article{
author = "Platanić-Arizanović, Lena and Gligorijević, Nikola and Cvijetić, Ilija and Mijatović, Aleksandar and Krstić-Ristivojević, Maja and Minić, Simeon and Nikolić-Kokić, Aleksandra and Miljević, Čedo and Nikolić, Milan",
year = "2023",
abstract = ": Packed with hemoglobin, an essential protein for oxygen transport, human erythrocytes
are a suitable model system for testing the pleiotropic effects of lipophilic drugs. Our study investigated the interaction between antipsychotic drugs clozapine, ziprasidone, sertindole, and human
hemoglobin under simulated physiological conditions. Analysis of protein fluorescence quenching
at different temperatures and data obtained from the van’t Hoff diagram and molecular docking
indicate that the interactions are static and that the tetrameric human hemoglobin has one binding site
for all drugs in the central cavity near αβ interfaces and is dominantly mediated through hydrophobic
forces. The association constants were lower-moderate strength (~104 M−1
), the highest observed
for clozapine (2.2 × 104 M−1 at 25 ◦C). The clozapine binding showed “friendly” effects: increased
α-helical content, a higher melting point, and protein protection from free radical-mediated oxidation.
On the other hand, bound ziprasidone and sertindole had a slightly pro-oxidative effect, increasing
ferrihemoglobin content, a possible “foe”. Since the interaction of proteins with drugs plays a vital
role in their pharmacokinetic and pharmacodynamic properties, the physiological significance of the
obtained findings is briefly discussed.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?",
number = "10",
volume = "24",
doi = "10.3390/ijms24108921",
pages = "8921"
}

Platanić-Arizanović, L., Gligorijević, N., Cvijetić, I., Mijatović, A., Krstić-Ristivojević, M., Minić, S., Nikolić-Kokić, A., Miljević, Č.,& Nikolić, M.. (2023). Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?. in International Journal of Molecular Sciences
Basel: MDPI., 24(10), 8921.
https://doi.org/10.3390/ijms24108921

Platanić-Arizanović L, Gligorijević N, Cvijetić I, Mijatović A, Krstić-Ristivojević M, Minić S, Nikolić-Kokić A, Miljević Č, Nikolić M. Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?. in International Journal of Molecular Sciences. 2023;24(10):8921.
doi:10.3390/ijms24108921 .

Platanić-Arizanović, Lena, Gligorijević, Nikola, Cvijetić, Ilija, Mijatović, Aleksandar, Krstić-Ristivojević, Maja, Minić, Simeon, Nikolić-Kokić, Aleksandra, Miljević, Čedo, Nikolić, Milan, "Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?" in International Journal of Molecular Sciences, 24, no. 10 (2023):8921,
https://doi.org/10.3390/ijms24108921 . .

TY  - JOUR
AU  - Milosavljević, Filip
AU  - Brusini, Irene
AU  - Atanasov, Andrea
AU  - Manojlović, Marina
AU  - Vučić, Marija
AU  - Oreščanin-Dušić, Zorana
AU  - Brkljačić, Jelena
AU  - Miljević, Čedo
AU  - Nikolić-Kokić, Aleksandra
AU  - Blagojević, Duško
AU  - Wang, Chunliang
AU  - Damberg, Peter
AU  - Pešić, Vesna
AU  - Tyndale, Rachel F.
AU  - Ingelman-Sundberg, Magnus
AU  - Jukić, Marin M.
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5758
AB  - Aims: CYP2C19 transgenic mouse expresses the human CYP2C19 gene in the liver and developing brain, and it exhibits altered neurodevelopment associated with impairments in emotionality and locomotion. Because the validation of new animal models is essential for the understanding of the aetiology and pathophysiology of movement disorders, the objective was to characterise motoric phenotype in CYP2C19 transgenic mice and to investigate its validity as a new animal model of ataxia.

Methods: The rotarod, paw-print and beam-walking tests were utilised to characterise the motoric phenotype. The volumes of 20 brain regions in CYP2C19 transgenic and wild-type mice were quantified by 9.4T gadolinium-enhanced post-mortem structural neuroimaging. Antioxidative enzymatic activity was quantified biochemically. Dopaminergic alterations were characterised by chromatographic quantification of concentrations of dopamine and its metabolites and by subsequent immunohistochemical analyses. The beam-walking test was repeated after the treatment with dopamine receptor antagonists ecopipam and raclopride.

Results: CYP2C19 transgenic mice exhibit abnormal, unilateral ataxia-like gait, clasping reflex and 5.6-fold more paw-slips in the beam-walking test; the motoric phenotype was more pronounced in youth. Transgenic mice exhibited a profound reduction of 12% in cerebellar volume and a moderate reduction of 4% in hippocampal volume; both regions exhibited an increased antioxidative enzyme activity. CYP2C19 mice were hyperdopaminergic; however, the motoric impairment was not ameliorated by dopamine receptor antagonists, and there was no alteration in the number of midbrain dopaminergic neurons in CYP2C19 mice.

Conclusions: Humanised CYP2C19 transgenic mice exhibit altered gait and functional motoric impairments; this phenotype is likely caused by an aberrant cerebellar development.
PB  - Hoboken: Wiley
T2  - Neuropathology and Applied Neurobiology
T1  - The humanised CYP2C19 transgenic mouse exhibits cerebellar atrophy and movement impairment reminiscent of ataxia
IS  - 1
VL  - 49
DO  - 10.1111/nan.12867
SP  - e12867
ER  - 

@article{
author = "Milosavljević, Filip and Brusini, Irene and Atanasov, Andrea and Manojlović, Marina and Vučić, Marija and Oreščanin-Dušić, Zorana and Brkljačić, Jelena and Miljević, Čedo and Nikolić-Kokić, Aleksandra and Blagojević, Duško and Wang, Chunliang and Damberg, Peter and Pešić, Vesna and Tyndale, Rachel F. and Ingelman-Sundberg, Magnus and Jukić, Marin M.",
year = "2023",
abstract = "Aims: CYP2C19 transgenic mouse expresses the human CYP2C19 gene in the liver and developing brain, and it exhibits altered neurodevelopment associated with impairments in emotionality and locomotion. Because the validation of new animal models is essential for the understanding of the aetiology and pathophysiology of movement disorders, the objective was to characterise motoric phenotype in CYP2C19 transgenic mice and to investigate its validity as a new animal model of ataxia.

Methods: The rotarod, paw-print and beam-walking tests were utilised to characterise the motoric phenotype. The volumes of 20 brain regions in CYP2C19 transgenic and wild-type mice were quantified by 9.4T gadolinium-enhanced post-mortem structural neuroimaging. Antioxidative enzymatic activity was quantified biochemically. Dopaminergic alterations were characterised by chromatographic quantification of concentrations of dopamine and its metabolites and by subsequent immunohistochemical analyses. The beam-walking test was repeated after the treatment with dopamine receptor antagonists ecopipam and raclopride.

Results: CYP2C19 transgenic mice exhibit abnormal, unilateral ataxia-like gait, clasping reflex and 5.6-fold more paw-slips in the beam-walking test; the motoric phenotype was more pronounced in youth. Transgenic mice exhibited a profound reduction of 12% in cerebellar volume and a moderate reduction of 4% in hippocampal volume; both regions exhibited an increased antioxidative enzyme activity. CYP2C19 mice were hyperdopaminergic; however, the motoric impairment was not ameliorated by dopamine receptor antagonists, and there was no alteration in the number of midbrain dopaminergic neurons in CYP2C19 mice.

Conclusions: Humanised CYP2C19 transgenic mice exhibit altered gait and functional motoric impairments; this phenotype is likely caused by an aberrant cerebellar development.",
publisher = "Hoboken: Wiley",
journal = "Neuropathology and Applied Neurobiology",
title = "The humanised CYP2C19 transgenic mouse exhibits cerebellar atrophy and movement impairment reminiscent of ataxia",
number = "1",
volume = "49",
doi = "10.1111/nan.12867",
pages = "e12867"
}

Milosavljević, F., Brusini, I., Atanasov, A., Manojlović, M., Vučić, M., Oreščanin-Dušić, Z., Brkljačić, J., Miljević, Č., Nikolić-Kokić, A., Blagojević, D., Wang, C., Damberg, P., Pešić, V., Tyndale, R. F., Ingelman-Sundberg, M.,& Jukić, M. M.. (2023). The humanised CYP2C19 transgenic mouse exhibits cerebellar atrophy and movement impairment reminiscent of ataxia. in Neuropathology and Applied Neurobiology
Hoboken: Wiley., 49(1), e12867.
https://doi.org/10.1111/nan.12867

Milosavljević F, Brusini I, Atanasov A, Manojlović M, Vučić M, Oreščanin-Dušić Z, Brkljačić J, Miljević Č, Nikolić-Kokić A, Blagojević D, Wang C, Damberg P, Pešić V, Tyndale RF, Ingelman-Sundberg M, Jukić MM. The humanised CYP2C19 transgenic mouse exhibits cerebellar atrophy and movement impairment reminiscent of ataxia. in Neuropathology and Applied Neurobiology. 2023;49(1):e12867.
doi:10.1111/nan.12867 .

Milosavljević, Filip, Brusini, Irene, Atanasov, Andrea, Manojlović, Marina, Vučić, Marija, Oreščanin-Dušić, Zorana, Brkljačić, Jelena, Miljević, Čedo, Nikolić-Kokić, Aleksandra, Blagojević, Duško, Wang, Chunliang, Damberg, Peter, Pešić, Vesna, Tyndale, Rachel F., Ingelman-Sundberg, Magnus, Jukić, Marin M., "The humanised CYP2C19 transgenic mouse exhibits cerebellar atrophy and movement impairment reminiscent of ataxia" in Neuropathology and Applied Neurobiology, 49, no. 1 (2023):e12867,
https://doi.org/10.1111/nan.12867 . .

TY  - CONF
AU  - Grahovac, Tanja
AU  - Tatalović, Nikola
AU  - Vidonja Uzelac, Teodora
AU  - Slavić, Marija
AU  - Nikolić-Kokić, Aleksandra
AU  - Blagojević, Duško
AU  - Oreščanin-Dušić, Zorana
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5848
AB  - Женке пацова имају хормонски контролисан еструсни циклус који изазива регуларне цикличне ткивне и ћелијске промене. Стога, експерименти који се изводе на женкама треба да укључују проверу фазе циклуса и рад на јединкама које су у истој фази. Уобичајено је да се узимају женке у еструсу, али како еструсна фаза траје 15-24 h, женке третиране у еструсу после 6 h ће бити и даље у еструсу у већини случајева, али већ после 24 h су у метаеструсу. Наши претходни резултати показују да ефекти на женкама пацова зависе од фазе циклуса када је апликација фармаколошки активним агенсом урађена. Како је изоловани утерус један од фармаколошких ex vivo модела избора испитивања деловања фармаколошки активних супстанци, укључујући и редокс активне, промене у утерусу директно подложне цикличности могу утицати на ефективност учинка, те и давати варијабилне резултате активности. Стога смо у овом раду мерили активност антиоксидативних ензима (SOD, CAT, GSH-Px и GR) у утерусу у различитим фазама еструсног циклуса. Утеруси у еструсу имају нижу SOD2 и вишу GSH-Px активност у поређењу са другим фазама. Активност GR у еструсу и проеструсу су биле више у поређењу са метаеструсом и диеструсом. Ове промене су у вези и са хормоналним и са редокс статусом утеруса током циклуса. Наши резултати показују да физиолошки, а посебно редокс одговор на екстерне стимулусе може бити другачији у зависности од фазе еструсног циклуса.
AB  - Ženke pacova imaju hormonski kontrolisan estrusni ciklus koji izaziva regularne ciklične tkivne i ćelijske promene. Stoga, eksperimenti koji se izvode na ženkama treba da uključuje proveru faze ciklusa i rad na jedinkama koje su u istoj fazi. Uobičajeno je da se uzimaju ženke u estrusu, ali kako estrusna faza traje 15-24 h, ženke tretirane u estrusu posle 6 h će biti i dalje u estrusu u većini slučajeva, ali već posle 24 h su u metaestrusu. Naši prethodni rezultati pokazuju da efekti na ženkama pacova zavise od faze ciklusa kada je aplikacija farmakološki aktivnim agensom urađena. Kako je izolovani uterus jedan od farmakoloških ex vivo modela izbora ispitivanja delovanja farmakološki aktivnih supstanci, uključujući i redoks aktivne, promene u uterusu direktno podložne cikličnosti mogu uticati na efektivnost učinka, te i davati varijabilne rezultate aktivnosti. Stoga smo u ovom radu merili aktivnost antioksidativnih enzima (SOD, CAT, GSH-Px и GR) u uterusu u različitim fazama estrusnog ciklusa. Uterusi u estrusu imaju nižu SOD2 i višu GSH-Px aktivnost u poređenju sa drugim fazama. Aktivnost GR u estrusu i proestrusu su bile više u poređenju sa metaestrusom i diestrusom. Ove promene su u vezi i sa hormonalnim i sa redoks statusom uterusa tokom ciklusa. Naši rezultati pokazuju da fiziološki, a posebno redoks odgovor na eksterne stimuluse može biti drugačiji u zavisnosti od faze estrusnog ciklusa.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Активност антиоксидативних ензима у утерусу је зависна од еструсног циклуса
T1  - Aktivnost antioksidativnih enzima u uterusu je zavisna od estrusnog ciklusa
SP  - 390
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5848
ER  - 

@conference{
author = "Grahovac, Tanja and Tatalović, Nikola and Vidonja Uzelac, Teodora and Slavić, Marija and Nikolić-Kokić, Aleksandra and Blagojević, Duško and Oreščanin-Dušić, Zorana",
year = "2022",
abstract = "Женке пацова имају хормонски контролисан еструсни циклус који изазива регуларне цикличне ткивне и ћелијске промене. Стога, експерименти који се изводе на женкама треба да укључују проверу фазе циклуса и рад на јединкама које су у истој фази. Уобичајено је да се узимају женке у еструсу, али како еструсна фаза траје 15-24 h, женке третиране у еструсу после 6 h ће бити и даље у еструсу у већини случајева, али већ после 24 h су у метаеструсу. Наши претходни резултати показују да ефекти на женкама пацова зависе од фазе циклуса када је апликација фармаколошки активним агенсом урађена. Како је изоловани утерус један од фармаколошких ex vivo модела избора испитивања деловања фармаколошки активних супстанци, укључујући и редокс активне, промене у утерусу директно подложне цикличности могу утицати на ефективност учинка, те и давати варијабилне резултате активности. Стога смо у овом раду мерили активност антиоксидативних ензима (SOD, CAT, GSH-Px и GR) у утерусу у различитим фазама еструсног циклуса. Утеруси у еструсу имају нижу SOD2 и вишу GSH-Px активност у поређењу са другим фазама. Активност GR у еструсу и проеструсу су биле више у поређењу са метаеструсом и диеструсом. Ове промене су у вези и са хормоналним и са редокс статусом утеруса током циклуса. Наши резултати показују да физиолошки, а посебно редокс одговор на екстерне стимулусе може бити другачији у зависности од фазе еструсног циклуса., Ženke pacova imaju hormonski kontrolisan estrusni ciklus koji izaziva regularne ciklične tkivne i ćelijske promene. Stoga, eksperimenti koji se izvode na ženkama treba da uključuje proveru faze ciklusa i rad na jedinkama koje su u istoj fazi. Uobičajeno je da se uzimaju ženke u estrusu, ali kako estrusna faza traje 15-24 h, ženke tretirane u estrusu posle 6 h će biti i dalje u estrusu u većini slučajeva, ali već posle 24 h su u metaestrusu. Naši prethodni rezultati pokazuju da efekti na ženkama pacova zavise od faze ciklusa kada je aplikacija farmakološki aktivnim agensom urađena. Kako je izolovani uterus jedan od farmakoloških ex vivo modela izbora ispitivanja delovanja farmakološki aktivnih supstanci, uključujući i redoks aktivne, promene u uterusu direktno podložne cikličnosti mogu uticati na efektivnost učinka, te i davati varijabilne rezultate aktivnosti. Stoga smo u ovom radu merili aktivnost antioksidativnih enzima (SOD, CAT, GSH-Px и GR) u uterusu u različitim fazama estrusnog ciklusa. Uterusi u estrusu imaju nižu SOD2 i višu GSH-Px aktivnost u poređenju sa drugim fazama. Aktivnost GR u estrusu i proestrusu su bile više u poređenju sa metaestrusom i diestrusom. Ove promene su u vezi i sa hormonalnim i sa redoks statusom uterusa tokom ciklusa. Naši rezultati pokazuju da fiziološki, a posebno redoks odgovor na eksterne stimuluse može biti drugačiji u zavisnosti od faze estrusnog ciklusa.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Активност антиоксидативних ензима у утерусу је зависна од еструсног циклуса, Aktivnost antioksidativnih enzima u uterusu je zavisna od estrusnog ciklusa",
pages = "390",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5848"
}

Grahovac, T., Tatalović, N., Vidonja Uzelac, T., Slavić, M., Nikolić-Kokić, A., Blagojević, D.,& Oreščanin-Dušić, Z.. (2022). Активност антиоксидативних ензима у утерусу је зависна од еструсног циклуса. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society., 390.
https://hdl.handle.net/21.15107/rcub_ibiss_5848

Grahovac T, Tatalović N, Vidonja Uzelac T, Slavić M, Nikolić-Kokić A, Blagojević D, Oreščanin-Dušić Z. Активност антиоксидативних ензима у утерусу је зависна од еструсног циклуса. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;:390.
https://hdl.handle.net/21.15107/rcub_ibiss_5848 .

Grahovac, Tanja, Tatalović, Nikola, Vidonja Uzelac, Teodora, Slavić, Marija, Nikolić-Kokić, Aleksandra, Blagojević, Duško, Oreščanin-Dušić, Zorana, "Активност антиоксидативних ензима у утерусу је зависна од еструсног циклуса" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022):390,
https://hdl.handle.net/21.15107/rcub_ibiss_5848 .

TY  - JOUR
AU  - Miletić, Srđan
AU  - Nikolić-Kokić, Aleksandra
AU  - Jovanović, Dara
AU  - Žerađanin, Aleksandra
AU  - Joksimović, Kristina
AU  - Avdalović, Jelena
AU  - Spasić, Snežana
PY  - 2022
UR  - https://link.springer.com/10.1134/S1068162023010193
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5360
AB  - In this research, the antioxidant activity of acidic and alkaline hydrolyzates of pectin isolated from quince (Cydonia oblonga) was investigated. The antioxidant role of quince has been known since before, but so far few papers have been published dealing with the antioxidant role of pectin hydrolyzate. In this study, quince pectin was isolated and hydrolyzed by acid and alkaline hydrolysis. Antioxidant activity was examined using a number of different methods, such as 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity, Cupric Ion Reducing Antioxidant Capacity (CUPRAC) assay, iron chelators, and oxygen radical absorption capacity (ORAC). Our results, especially the ORAC test, show that depolymerization produces the most substances with antioxidant release properties in the alkaline hydrolysis of quince pectin.
PB  - Pleiades Publishing
T2  - Russian Journal of Bioorganic Chemistry
T1  - Investigation of the Antioxidant Role of Acidic and Alkaline Hydrolysates of Pectin Isolated from Quince (Cydonia oblonga)
DO  - 10.1134/S1068162023010193
ER  - 

@article{
author = "Miletić, Srđan and Nikolić-Kokić, Aleksandra and Jovanović, Dara and Žerađanin, Aleksandra and Joksimović, Kristina and Avdalović, Jelena and Spasić, Snežana",
year = "2022",
abstract = "In this research, the antioxidant activity of acidic and alkaline hydrolyzates of pectin isolated from quince (Cydonia oblonga) was investigated. The antioxidant role of quince has been known since before, but so far few papers have been published dealing with the antioxidant role of pectin hydrolyzate. In this study, quince pectin was isolated and hydrolyzed by acid and alkaline hydrolysis. Antioxidant activity was examined using a number of different methods, such as 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity, Cupric Ion Reducing Antioxidant Capacity (CUPRAC) assay, iron chelators, and oxygen radical absorption capacity (ORAC). Our results, especially the ORAC test, show that depolymerization produces the most substances with antioxidant release properties in the alkaline hydrolysis of quince pectin.",
publisher = "Pleiades Publishing",
journal = "Russian Journal of Bioorganic Chemistry",
title = "Investigation of the Antioxidant Role of Acidic and Alkaline Hydrolysates of Pectin Isolated from Quince (Cydonia oblonga)",
doi = "10.1134/S1068162023010193"
}

Miletić, S., Nikolić-Kokić, A., Jovanović, D., Žerađanin, A., Joksimović, K., Avdalović, J.,& Spasić, S.. (2022). Investigation of the Antioxidant Role of Acidic and Alkaline Hydrolysates of Pectin Isolated from Quince (Cydonia oblonga). in Russian Journal of Bioorganic Chemistry
Pleiades Publishing..
https://doi.org/10.1134/S1068162023010193

Miletić S, Nikolić-Kokić A, Jovanović D, Žerađanin A, Joksimović K, Avdalović J, Spasić S. Investigation of the Antioxidant Role of Acidic and Alkaline Hydrolysates of Pectin Isolated from Quince (Cydonia oblonga). in Russian Journal of Bioorganic Chemistry. 2022;.
doi:10.1134/S1068162023010193 .

Miletić, Srđan, Nikolić-Kokić, Aleksandra, Jovanović, Dara, Žerađanin, Aleksandra, Joksimović, Kristina, Avdalović, Jelena, Spasić, Snežana, "Investigation of the Antioxidant Role of Acidic and Alkaline Hydrolysates of Pectin Isolated from Quince (Cydonia oblonga)" in Russian Journal of Bioorganic Chemistry (2022),
https://doi.org/10.1134/S1068162023010193 . .

TY  - JOUR
AU  - Nikolić-Kokić, Aleksandra
AU  - Tatalović, Nikola
AU  - Brkljačić, Jelena
AU  - Mijović, Milica
AU  - Nestorović, Vojkan
AU  - Mijušković, Ana
AU  - Oreščanin-Dušić, Zorana
AU  - Vidonja Uzelac, Teodora
AU  - Nikolić, Milan
AU  - Spasić, Snežana
AU  - Blagojević, Duško
AU  - Miljević, Čedo
PY  - 2022
UR  - https://www.mdpi.com/1422-0067/23/22/13698
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5344
AB  - Sexual dysfunction, as a noticeable adverse effect of atypical antipsychotic drugs (APDs) for the treatment of schizophrenia, has not been investigated in detail. A study was undertaken to investigate whether 28-day long treatment with clozapine, ziprasidone or sertindole (using a recommended daily dose for atypical antipsychotic therapy), induced histopathological changes both in rat testicles and prostate, changed the activity of the antioxidant defence system and altered blood testosterone and prolactin. Clozapine, ziprasidone and sertindole induced histopathological changes in rat testicular tissue, which could be attributed to a disturbed testicular antioxidant defence system in addition to an altered prolactin to testosterone ratio. None of the APD treatments induced histopathological changes in prostate. Our results demonstrate that APDs have the capacity to change both redox and endocrinological balance. One or both outcomes could underline testicular degeneration and disturbed spermatogenesis.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Antipsychotic Drug-Mediated Adverse Effects on Rat Testicles May Be Caused by Altered Redox and Hormonal Homeostasis
IS  - 22
VL  - 23
DO  - 10.3390/ijms232213698
SP  - 13698
ER  - 

@article{
author = "Nikolić-Kokić, Aleksandra and Tatalović, Nikola and Brkljačić, Jelena and Mijović, Milica and Nestorović, Vojkan and Mijušković, Ana and Oreščanin-Dušić, Zorana and Vidonja Uzelac, Teodora and Nikolić, Milan and Spasić, Snežana and Blagojević, Duško and Miljević, Čedo",
year = "2022",
abstract = "Sexual dysfunction, as a noticeable adverse effect of atypical antipsychotic drugs (APDs) for the treatment of schizophrenia, has not been investigated in detail. A study was undertaken to investigate whether 28-day long treatment with clozapine, ziprasidone or sertindole (using a recommended daily dose for atypical antipsychotic therapy), induced histopathological changes both in rat testicles and prostate, changed the activity of the antioxidant defence system and altered blood testosterone and prolactin. Clozapine, ziprasidone and sertindole induced histopathological changes in rat testicular tissue, which could be attributed to a disturbed testicular antioxidant defence system in addition to an altered prolactin to testosterone ratio. None of the APD treatments induced histopathological changes in prostate. Our results demonstrate that APDs have the capacity to change both redox and endocrinological balance. One or both outcomes could underline testicular degeneration and disturbed spermatogenesis.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Antipsychotic Drug-Mediated Adverse Effects on Rat Testicles May Be Caused by Altered Redox and Hormonal Homeostasis",
number = "22",
volume = "23",
doi = "10.3390/ijms232213698",
pages = "13698"
}

Nikolić-Kokić, A., Tatalović, N., Brkljačić, J., Mijović, M., Nestorović, V., Mijušković, A., Oreščanin-Dušić, Z., Vidonja Uzelac, T., Nikolić, M., Spasić, S., Blagojević, D.,& Miljević, Č.. (2022). Antipsychotic Drug-Mediated Adverse Effects on Rat Testicles May Be Caused by Altered Redox and Hormonal Homeostasis. in International Journal of Molecular Sciences
Basel: MDPI., 23(22), 13698.
https://doi.org/10.3390/ijms232213698

Nikolić-Kokić A, Tatalović N, Brkljačić J, Mijović M, Nestorović V, Mijušković A, Oreščanin-Dušić Z, Vidonja Uzelac T, Nikolić M, Spasić S, Blagojević D, Miljević Č. Antipsychotic Drug-Mediated Adverse Effects on Rat Testicles May Be Caused by Altered Redox and Hormonal Homeostasis. in International Journal of Molecular Sciences. 2022;23(22):13698.
doi:10.3390/ijms232213698 .

Nikolić-Kokić, Aleksandra, Tatalović, Nikola, Brkljačić, Jelena, Mijović, Milica, Nestorović, Vojkan, Mijušković, Ana, Oreščanin-Dušić, Zorana, Vidonja Uzelac, Teodora, Nikolić, Milan, Spasić, Snežana, Blagojević, Duško, Miljević, Čedo, "Antipsychotic Drug-Mediated Adverse Effects on Rat Testicles May Be Caused by Altered Redox and Hormonal Homeostasis" in International Journal of Molecular Sciences, 23, no. 22 (2022):13698,
https://doi.org/10.3390/ijms232213698 . .

TY  - JOUR
AU  - Đurović, Dijana
AU  - Đorđević, Zorica
AU  - Mugoša, Boban
AU  - Bajić, Borko
AU  - Nikolić-Kokić, Aleksandra
AU  - Miletić, Srđan
AU  - Spasić, Snežana
PY  - 2022
UR  - https://onlinelibrary.wiley.com/doi/10.1002/ijgo.14370
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5104
AB  - OBJECTIVE In this study, iodine level in pregnant women of Montenegro and their needs for supplementation were investigated. METHODS A urinary iodine concentration (UIC) study of 326 pregnant women between September and December 2017 in three regions of Montenegro was performed. UIC was related to creatinine (UI/Cr ratio). RESULTS The median UIC (133 ± 5 μg/L) was indicative of iodine deficiency, as the WHO recommended UIC is 150-249 μg/L. The UI/Cr ratio (160 ± 6 μg/g creatinine) was just above the WHO/UNICEF/IGN recommendation. Approximately 50% of the surveyed women had a lower UIC than that recommended. CONCLUSION Iodine deficiency is present in pregnant women in Montenegro. Monitoring the UIC during routine analyses in pregnant women in Montenegro is recommended, along with iodine supplementation for individuals that need it.
PB  - Hoboken: Wiley
T2  - International Journal of Gynecology and Obstetrics
T1  - Half of expectant women in Montenegro show iodine deficiency, indicating that supplementation during pregnancy is necessary.
IS  - 2
VL  - 160
DO  - 10.1002/ijgo.14370
SP  - 691
EP  - 697
ER  - 

@article{
author = "Đurović, Dijana and Đorđević, Zorica and Mugoša, Boban and Bajić, Borko and Nikolić-Kokić, Aleksandra and Miletić, Srđan and Spasić, Snežana",
year = "2022",
abstract = "OBJECTIVE In this study, iodine level in pregnant women of Montenegro and their needs for supplementation were investigated. METHODS A urinary iodine concentration (UIC) study of 326 pregnant women between September and December 2017 in three regions of Montenegro was performed. UIC was related to creatinine (UI/Cr ratio). RESULTS The median UIC (133 ± 5 μg/L) was indicative of iodine deficiency, as the WHO recommended UIC is 150-249 μg/L. The UI/Cr ratio (160 ± 6 μg/g creatinine) was just above the WHO/UNICEF/IGN recommendation. Approximately 50% of the surveyed women had a lower UIC than that recommended. CONCLUSION Iodine deficiency is present in pregnant women in Montenegro. Monitoring the UIC during routine analyses in pregnant women in Montenegro is recommended, along with iodine supplementation for individuals that need it.",
publisher = "Hoboken: Wiley",
journal = "International Journal of Gynecology and Obstetrics",
title = "Half of expectant women in Montenegro show iodine deficiency, indicating that supplementation during pregnancy is necessary.",
number = "2",
volume = "160",
doi = "10.1002/ijgo.14370",
pages = "691-697"
}

Đurović, D., Đorđević, Z., Mugoša, B., Bajić, B., Nikolić-Kokić, A., Miletić, S.,& Spasić, S.. (2022). Half of expectant women in Montenegro show iodine deficiency, indicating that supplementation during pregnancy is necessary.. in International Journal of Gynecology and Obstetrics
Hoboken: Wiley., 160(2), 691-697.
https://doi.org/10.1002/ijgo.14370

Đurović D, Đorđević Z, Mugoša B, Bajić B, Nikolić-Kokić A, Miletić S, Spasić S. Half of expectant women in Montenegro show iodine deficiency, indicating that supplementation during pregnancy is necessary.. in International Journal of Gynecology and Obstetrics. 2022;160(2):691-697.
doi:10.1002/ijgo.14370 .

Đurović, Dijana, Đorđević, Zorica, Mugoša, Boban, Bajić, Borko, Nikolić-Kokić, Aleksandra, Miletić, Srđan, Spasić, Snežana, "Half of expectant women in Montenegro show iodine deficiency, indicating that supplementation during pregnancy is necessary." in International Journal of Gynecology and Obstetrics, 160, no. 2 (2022):691-697,
https://doi.org/10.1002/ijgo.14370 . .

TY  - JOUR
AU  - Tasić, Danica
AU  - Opačić, Miloš
AU  - Kovačević, Sanja
AU  - Nikolić-Kokić, Aleksandra
AU  - Dimitrijević, Milena
AU  - Nikolić, Dušan
AU  - Vojnović-Milutinović, Danijela
AU  - Blagojević, Duško
AU  - Đorđević, Ana
AU  - Brkljačić, Jelena
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5025
AB  - The effects of a fructose-rich diet and chronic stress on copper metabolism in the kidneys
are still understudied. We investigated whether fructose and/or chronic unpredictable stress modulate
copper metabolism in a way that affects redox homeostasis, thus contributing to progression
of metabolic disturbances in the kidney. We determined protein level of copper transporters,
chaperones, and cuproenzymes including cytochrome c oxidase, as well as antioxidant enzymes
function in the kidneys of male Wistar rats subjected to 20% liquid fructose supplementation
and/or chronic stress. Liquid fructose supplementation increased level of copper chaperone of
superoxide dismutase and decreased metallothionein level, while rendering the level of copper
importer and copper chaperones involved in copper delivery to mitochondria and trans Golgi
network unaffected. Stress had no effect on renal copper metabolism. The activity and expression
of renal antioxidant enzymes remained unaltered in all experimental groups. In conclusion, fructose,
independently of stress, decreased renal copper level, and modulated renal copper metabolism
as to preserve vital cellular function including mitochondrial energy production and antioxidative
defense, at the expense of intracellular copper storage.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Effects of Fructose and Stress on Rat Renal Copper Metabolism and Antioxidant Enzymes Function
IS  - 16
VL  - 23
DO  - 10.3390/ijms23169023
SP  - 9023
ER  - 

@article{
author = "Tasić, Danica and Opačić, Miloš and Kovačević, Sanja and Nikolić-Kokić, Aleksandra and Dimitrijević, Milena and Nikolić, Dušan and Vojnović-Milutinović, Danijela and Blagojević, Duško and Đorđević, Ana and Brkljačić, Jelena",
year = "2022",
abstract = "The effects of a fructose-rich diet and chronic stress on copper metabolism in the kidneys
are still understudied. We investigated whether fructose and/or chronic unpredictable stress modulate
copper metabolism in a way that affects redox homeostasis, thus contributing to progression
of metabolic disturbances in the kidney. We determined protein level of copper transporters,
chaperones, and cuproenzymes including cytochrome c oxidase, as well as antioxidant enzymes
function in the kidneys of male Wistar rats subjected to 20% liquid fructose supplementation
and/or chronic stress. Liquid fructose supplementation increased level of copper chaperone of
superoxide dismutase and decreased metallothionein level, while rendering the level of copper
importer and copper chaperones involved in copper delivery to mitochondria and trans Golgi
network unaffected. Stress had no effect on renal copper metabolism. The activity and expression
of renal antioxidant enzymes remained unaltered in all experimental groups. In conclusion, fructose,
independently of stress, decreased renal copper level, and modulated renal copper metabolism
as to preserve vital cellular function including mitochondrial energy production and antioxidative
defense, at the expense of intracellular copper storage.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Effects of Fructose and Stress on Rat Renal Copper Metabolism and Antioxidant Enzymes Function",
number = "16",
volume = "23",
doi = "10.3390/ijms23169023",
pages = "9023"
}

Tasić, D., Opačić, M., Kovačević, S., Nikolić-Kokić, A., Dimitrijević, M., Nikolić, D., Vojnović-Milutinović, D., Blagojević, D., Đorđević, A.,& Brkljačić, J.. (2022). Effects of Fructose and Stress on Rat Renal Copper Metabolism and Antioxidant Enzymes Function. in International Journal of Molecular Sciences
Basel: MDPI., 23(16), 9023.
https://doi.org/10.3390/ijms23169023

Tasić D, Opačić M, Kovačević S, Nikolić-Kokić A, Dimitrijević M, Nikolić D, Vojnović-Milutinović D, Blagojević D, Đorđević A, Brkljačić J. Effects of Fructose and Stress on Rat Renal Copper Metabolism and Antioxidant Enzymes Function. in International Journal of Molecular Sciences. 2022;23(16):9023.
doi:10.3390/ijms23169023 .

Tasić, Danica, Opačić, Miloš, Kovačević, Sanja, Nikolić-Kokić, Aleksandra, Dimitrijević, Milena, Nikolić, Dušan, Vojnović-Milutinović, Danijela, Blagojević, Duško, Đorđević, Ana, Brkljačić, Jelena, "Effects of Fructose and Stress on Rat Renal Copper Metabolism and Antioxidant Enzymes Function" in International Journal of Molecular Sciences, 23, no. 16 (2022):9023,
https://doi.org/10.3390/ijms23169023 . .

TY  - CONF
AU  - Tatalović, Nikola
AU  - Nikolić-Kokić, Aleksandra
AU  - Oreščanin Dušić, Zorana
AU  - Vidonja Uzelac, Teodora
AU  - Grahovac, Tanja
AU  - Blagojević, Duško
AU  - Miljević, Čedo
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5186
AB  - Atypical antipsychotic drugs (APDs) are being used to treat
acute psychotic episodes in schizophrenia and schizophrenia-related
diseases as well as a variety of nonpsychotic disorders.
Despite their effectiveness, we showed that APDs clozapine
(CLO), ziprasidone (ZIP) and sertindole (SER) increased oxidative
stress and reduced antioxidative defence capacity in rat kidneys
and heart. Given the scarcity of data about CLO, ZIP and
SER actions on the brain redox homeostasis, the goal of current
study was to investigate their impact on antioxidant enzymes:
total superoxide dismutase (SOD), catalase (CAT), glutathione
peroxidase (GPx) and glutathione reductase (GR) in brain of 3 month old male Wistar rats treated daily via intubation with
water (control group), CLO (45 mg/kg/day), ZIP (20 mg/kg/day)
or SER (2.5 mg/kg/day) for 6 weeks. There were no significant
changes in investigated parameters in CLO and ZIP groups.
However, in SER group the total SOD activity was decreased
while CAT and GPx activities were increased compared to control
group (One-way ANOVA with Tukey’s HSD test, P < 0.05).
Since both CAT and GPx catalyze decomposition of H2O2, their
increased activity in SER group suggests an elevated peroxide
pressure. This conclusion can be strengthened since the activity
of SOD can be decreased by elevated concentration of H2O2.
Our results suggest that SER could cause a redox imbalance in
brain with possible negative effects on mitochondrial respiration
and neural tissue metabolism. *The authors marked with an
asterisk equally contributed to the work.
PB  - Hoboken : John Wiley & Sons Ltd
C3  - The Biochemistry Global Summit: 25th IUBMB Congress: 46th FEBS Congress: 15th PABMB Congress; 2022 Jul 9-14; Lisbon, Portugal
T1  - Chronic treatment with sertindole, but not clozapine and ziprasidone, affects redox homeostasis in brain of male rats
DO  - 10.1002/2211-5463.13440
SP  - 299
ER  - 

@conference{
author = "Tatalović, Nikola and Nikolić-Kokić, Aleksandra and Oreščanin Dušić, Zorana and Vidonja Uzelac, Teodora and Grahovac, Tanja and Blagojević, Duško and Miljević, Čedo",
year = "2022",
abstract = "Atypical antipsychotic drugs (APDs) are being used to treat
acute psychotic episodes in schizophrenia and schizophrenia-related
diseases as well as a variety of nonpsychotic disorders.
Despite their effectiveness, we showed that APDs clozapine
(CLO), ziprasidone (ZIP) and sertindole (SER) increased oxidative
stress and reduced antioxidative defence capacity in rat kidneys
and heart. Given the scarcity of data about CLO, ZIP and
SER actions on the brain redox homeostasis, the goal of current
study was to investigate their impact on antioxidant enzymes:
total superoxide dismutase (SOD), catalase (CAT), glutathione
peroxidase (GPx) and glutathione reductase (GR) in brain of 3 month old male Wistar rats treated daily via intubation with
water (control group), CLO (45 mg/kg/day), ZIP (20 mg/kg/day)
or SER (2.5 mg/kg/day) for 6 weeks. There were no significant
changes in investigated parameters in CLO and ZIP groups.
However, in SER group the total SOD activity was decreased
while CAT and GPx activities were increased compared to control
group (One-way ANOVA with Tukey’s HSD test, P < 0.05).
Since both CAT and GPx catalyze decomposition of H2O2, their
increased activity in SER group suggests an elevated peroxide
pressure. This conclusion can be strengthened since the activity
of SOD can be decreased by elevated concentration of H2O2.
Our results suggest that SER could cause a redox imbalance in
brain with possible negative effects on mitochondrial respiration
and neural tissue metabolism. *The authors marked with an
asterisk equally contributed to the work.",
publisher = "Hoboken : John Wiley & Sons Ltd",
journal = "The Biochemistry Global Summit: 25th IUBMB Congress: 46th FEBS Congress: 15th PABMB Congress; 2022 Jul 9-14; Lisbon, Portugal",
title = "Chronic treatment with sertindole, but not clozapine and ziprasidone, affects redox homeostasis in brain of male rats",
doi = "10.1002/2211-5463.13440",
pages = "299"
}

Tatalović, N., Nikolić-Kokić, A., Oreščanin Dušić, Z., Vidonja Uzelac, T., Grahovac, T., Blagojević, D.,& Miljević, Č.. (2022). Chronic treatment with sertindole, but not clozapine and ziprasidone, affects redox homeostasis in brain of male rats. in The Biochemistry Global Summit: 25th IUBMB Congress: 46th FEBS Congress: 15th PABMB Congress; 2022 Jul 9-14; Lisbon, Portugal
Hoboken : John Wiley & Sons Ltd., 299.
https://doi.org/10.1002/2211-5463.13440

Tatalović N, Nikolić-Kokić A, Oreščanin Dušić Z, Vidonja Uzelac T, Grahovac T, Blagojević D, Miljević Č. Chronic treatment with sertindole, but not clozapine and ziprasidone, affects redox homeostasis in brain of male rats. in The Biochemistry Global Summit: 25th IUBMB Congress: 46th FEBS Congress: 15th PABMB Congress; 2022 Jul 9-14; Lisbon, Portugal. 2022;:299.
doi:10.1002/2211-5463.13440 .

Tatalović, Nikola, Nikolić-Kokić, Aleksandra, Oreščanin Dušić, Zorana, Vidonja Uzelac, Teodora, Grahovac, Tanja, Blagojević, Duško, Miljević, Čedo, "Chronic treatment with sertindole, but not clozapine and ziprasidone, affects redox homeostasis in brain of male rats" in The Biochemistry Global Summit: 25th IUBMB Congress: 46th FEBS Congress: 15th PABMB Congress; 2022 Jul 9-14; Lisbon, Portugal (2022):299,
https://doi.org/10.1002/2211-5463.13440 . .

TY  - CONF
AU  - Grahovac, Tanja
AU  - Vidonja Uzelac, Teodora
AU  - Nikolić-Kokić, Aleksandra
AU  - Oreščanin Dušić, Zorana
AU  - Blagojević, Duško
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5185
AB  - Redox-mediated mechanisms play an important role in regulating
smooth muscle contractility and depend on subtle redox homeostasis
maintaining. Redox homeostasis in cells is obtained by
the activity of antioxidant enzymes. Among them, glutathione
reductase constantly reduces oxidized glutathione, providing a
favorable cellular redox milieu. The aim of this study was to
examine whether, to what extent and in what way changes in
smooth muscle contractility occurred in conditions when glutathione
reductase activity was changed. The experiments were
performed on isolated ileum of male Wistar rats, electrically stimulated
and treated with cumulative doses of carmustine, a glutathione
reductase inhibitor. The activity of antioxidant enzymes(catalase, glutathione reductase and glutathione peroxidase, as
well as the amount of total SH groups and glutathione) was
determined in treated ileum. The addition of carmustine inhibited
glutathione reductase activity and decreased amplitude and frequency
of electrically stimulated ileum. The results showed that
glutathione reductase activity and maintenance of highly reductive
cellular environment were essential to contractility processes.
PB  - Hoboken : John Wiley & Sons Ltd
C3  - The Biochemistry Global Summit: 25th IUBMB Congress: 46th FEBS Congress: 15th PABMB Congress; 2022 Jul 9-14; Lisbon, Portugal
T1  - Cellular redox homeostasis mediates contractility of isolated ileum of male Wistar rats
DO  - 10.1002/2211-5463.13440
SP  - 220
EP  - 221
ER  - 

@conference{
author = "Grahovac, Tanja and Vidonja Uzelac, Teodora and Nikolić-Kokić, Aleksandra and Oreščanin Dušić, Zorana and Blagojević, Duško",
year = "2022",
abstract = "Redox-mediated mechanisms play an important role in regulating
smooth muscle contractility and depend on subtle redox homeostasis
maintaining. Redox homeostasis in cells is obtained by
the activity of antioxidant enzymes. Among them, glutathione
reductase constantly reduces oxidized glutathione, providing a
favorable cellular redox milieu. The aim of this study was to
examine whether, to what extent and in what way changes in
smooth muscle contractility occurred in conditions when glutathione
reductase activity was changed. The experiments were
performed on isolated ileum of male Wistar rats, electrically stimulated
and treated with cumulative doses of carmustine, a glutathione
reductase inhibitor. The activity of antioxidant enzymes(catalase, glutathione reductase and glutathione peroxidase, as
well as the amount of total SH groups and glutathione) was
determined in treated ileum. The addition of carmustine inhibited
glutathione reductase activity and decreased amplitude and frequency
of electrically stimulated ileum. The results showed that
glutathione reductase activity and maintenance of highly reductive
cellular environment were essential to contractility processes.",
publisher = "Hoboken : John Wiley & Sons Ltd",
journal = "The Biochemistry Global Summit: 25th IUBMB Congress: 46th FEBS Congress: 15th PABMB Congress; 2022 Jul 9-14; Lisbon, Portugal",
title = "Cellular redox homeostasis mediates contractility of isolated ileum of male Wistar rats",
doi = "10.1002/2211-5463.13440",
pages = "220-221"
}

Grahovac, T., Vidonja Uzelac, T., Nikolić-Kokić, A., Oreščanin Dušić, Z.,& Blagojević, D.. (2022). Cellular redox homeostasis mediates contractility of isolated ileum of male Wistar rats. in The Biochemistry Global Summit: 25th IUBMB Congress: 46th FEBS Congress: 15th PABMB Congress; 2022 Jul 9-14; Lisbon, Portugal
Hoboken : John Wiley & Sons Ltd., 220-221.
https://doi.org/10.1002/2211-5463.13440

Grahovac T, Vidonja Uzelac T, Nikolić-Kokić A, Oreščanin Dušić Z, Blagojević D. Cellular redox homeostasis mediates contractility of isolated ileum of male Wistar rats. in The Biochemistry Global Summit: 25th IUBMB Congress: 46th FEBS Congress: 15th PABMB Congress; 2022 Jul 9-14; Lisbon, Portugal. 2022;:220-221.
doi:10.1002/2211-5463.13440 .

Grahovac, Tanja, Vidonja Uzelac, Teodora, Nikolić-Kokić, Aleksandra, Oreščanin Dušić, Zorana, Blagojević, Duško, "Cellular redox homeostasis mediates contractility of isolated ileum of male Wistar rats" in The Biochemistry Global Summit: 25th IUBMB Congress: 46th FEBS Congress: 15th PABMB Congress; 2022 Jul 9-14; Lisbon, Portugal (2022):220-221,
https://doi.org/10.1002/2211-5463.13440 . .

TY  - JOUR
AU  - Platanić Arizanović, Lena
AU  - Nikolić-Kokić, Aleksandra
AU  - Brkljačić, Jelena
AU  - Tatalović, Nikola
AU  - Miler, Marko
AU  - Oreščanin Dušić, Zorana
AU  - Vidonja Uzelac, Teodora
AU  - Nikolić, Milan
AU  - Milošević, Verica
AU  - Blagojević, Duško
AU  - Spasić, Snežana
AU  - Miljević, Čedo
PY  - 2021
UR  - https://www.tandfonline.com/doi/abs/10.1080/15287394.2020.1844827
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4037
AB  - Chronic use of atypical antipsychotics may produce hepatic damage. Atypical antipsychotics, including clozapine, sertindole, and ziprasidone, are extensively metabolized by the liver and this process generates toxic-free radical metabolic intermediates which may contribute to liver damage. The aim of this study was to investigate whether clozapine, sertindole, or ziprasidone affected hepatic antioxidant defense enzymes which consequently led to disturbed redox homeostasis. The expression and activity of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and glutathione-S-transferases (GST) were measured in rat livers at doses corresponding to human antipsychotic therapy. Clozapine increased activity of SOD types 1 and 2, GR and GST, but reduced CAT activity. Sertindole elevated activities of both SODs. In ziprasidone-treated rats only decreased CAT activity was found. All three antipsychotics produced mild-to-moderate hepatic histopathological changes categorized as regenerative alterations. No apparent signs of immune cell infiltration, microvesicular or macrovesicular fatty change, or hepatocytes in mitosis were observed. In conclusion, a 4-week long daily treatment with clozapine, sertindole, or ziprasidone altered hepatic antioxidant enzyme activities and induced histopathological changes in liver. The most severe alterations were noted in clozapine-treated rats. Data indicate that redox disturbances may contribute to liver dysfunction after long-term atypical antipsychotic drug treatment.
PB  - Bellwether Publishing, Ltd.
T2  - Journal of Toxicology and Environmental Health, Part A
T1  - Effects of several atypical antipsychotics closapine, sertindole or ziprasidone on hepatic antioxidant enzymes: Possible role in drug-induced liver dysfunction
IS  - 4
VL  - 84
DO  - 10.1080/15287394.2020.1844827
SP  - 173
EP  - 182
ER  - 

@article{
author = "Platanić Arizanović, Lena and Nikolić-Kokić, Aleksandra and Brkljačić, Jelena and Tatalović, Nikola and Miler, Marko and Oreščanin Dušić, Zorana and Vidonja Uzelac, Teodora and Nikolić, Milan and Milošević, Verica and Blagojević, Duško and Spasić, Snežana and Miljević, Čedo",
year = "2021",
abstract = "Chronic use of atypical antipsychotics may produce hepatic damage. Atypical antipsychotics, including clozapine, sertindole, and ziprasidone, are extensively metabolized by the liver and this process generates toxic-free radical metabolic intermediates which may contribute to liver damage. The aim of this study was to investigate whether clozapine, sertindole, or ziprasidone affected hepatic antioxidant defense enzymes which consequently led to disturbed redox homeostasis. The expression and activity of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and glutathione-S-transferases (GST) were measured in rat livers at doses corresponding to human antipsychotic therapy. Clozapine increased activity of SOD types 1 and 2, GR and GST, but reduced CAT activity. Sertindole elevated activities of both SODs. In ziprasidone-treated rats only decreased CAT activity was found. All three antipsychotics produced mild-to-moderate hepatic histopathological changes categorized as regenerative alterations. No apparent signs of immune cell infiltration, microvesicular or macrovesicular fatty change, or hepatocytes in mitosis were observed. In conclusion, a 4-week long daily treatment with clozapine, sertindole, or ziprasidone altered hepatic antioxidant enzyme activities and induced histopathological changes in liver. The most severe alterations were noted in clozapine-treated rats. Data indicate that redox disturbances may contribute to liver dysfunction after long-term atypical antipsychotic drug treatment.",
publisher = "Bellwether Publishing, Ltd.",
journal = "Journal of Toxicology and Environmental Health, Part A",
title = "Effects of several atypical antipsychotics closapine, sertindole or ziprasidone on hepatic antioxidant enzymes: Possible role in drug-induced liver dysfunction",
number = "4",
volume = "84",
doi = "10.1080/15287394.2020.1844827",
pages = "173-182"
}

Platanić Arizanović, L., Nikolić-Kokić, A., Brkljačić, J., Tatalović, N., Miler, M., Oreščanin Dušić, Z., Vidonja Uzelac, T., Nikolić, M., Milošević, V., Blagojević, D., Spasić, S.,& Miljević, Č.. (2021). Effects of several atypical antipsychotics closapine, sertindole or ziprasidone on hepatic antioxidant enzymes: Possible role in drug-induced liver dysfunction. in Journal of Toxicology and Environmental Health, Part A
Bellwether Publishing, Ltd.., 84(4), 173-182.
https://doi.org/10.1080/15287394.2020.1844827

Platanić Arizanović L, Nikolić-Kokić A, Brkljačić J, Tatalović N, Miler M, Oreščanin Dušić Z, Vidonja Uzelac T, Nikolić M, Milošević V, Blagojević D, Spasić S, Miljević Č. Effects of several atypical antipsychotics closapine, sertindole or ziprasidone on hepatic antioxidant enzymes: Possible role in drug-induced liver dysfunction. in Journal of Toxicology and Environmental Health, Part A. 2021;84(4):173-182.
doi:10.1080/15287394.2020.1844827 .

Platanić Arizanović, Lena, Nikolić-Kokić, Aleksandra, Brkljačić, Jelena, Tatalović, Nikola, Miler, Marko, Oreščanin Dušić, Zorana, Vidonja Uzelac, Teodora, Nikolić, Milan, Milošević, Verica, Blagojević, Duško, Spasić, Snežana, Miljević, Čedo, "Effects of several atypical antipsychotics closapine, sertindole or ziprasidone on hepatic antioxidant enzymes: Possible role in drug-induced liver dysfunction" in Journal of Toxicology and Environmental Health, Part A, 84, no. 4 (2021):173-182,
https://doi.org/10.1080/15287394.2020.1844827 . .

TY  - JOUR
AU  - Kovačević, Sanja
AU  - Elaković, Ivana
AU  - Vojnović-Milutinović, Danijela
AU  - Nikolić-Kokić, Aleksandra
AU  - Blagojević, Duško
AU  - Matić, Gordana
AU  - Tappy, Luc
AU  - Đorđević, Ana
AU  - Brkljačić, Jelena
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4468
AB  - Background: Both fructose consumption and chronic stress contribute to the development of metabolic disorders.
The consequences of such combination are not fully understood.
Objective: We investigated whether fructose supplementation and chronic stress synergistically disturb hepatic lipid
and glucose metabolism. The role of energy sensing, redox, and inflammatory status during development of metabolic
disturbances was investigated.
Methods: Female Wistar rats, aged 2.5 mo, were divided into 4 experimental groups: control (C) fed a standard diet
(commercial food and drinking water); fructose (F) fed the same food and 10% fructose solution; stress (S) fed the
standard diet and subjected to chronic unpredictable stress and, stress + fructose (SF) combining conditions F and
S as above. Stress included daily stressors: cold water forced swimming, physical restraint, cold room, wet bedding,
rocking, switching, or tilting cages. After 9 wk, hepatic enzymes and transcription factors involved in gluconeogenesis,
lipogenesis, fatty acid oxidation, antioxidative defence, energy sensing, and cytokines were assessed by qPCR, Western
blotting, and spectrophotometry and analyzed by 2-factor ANOVA.
Results: Fructose increased AMP-activated protein kinase (AMPK) phosphorylation (40%; P < 0.05) and the ratio of
inhibitory phosphorylation to total acetyl-CoA carboxylase (46%; P < 0.01), and decreased sterol regulatory element
binding protein 1c nuclear translocation by 30% (P < 0.05) in F and SF compared with C rats. Increased phosPck
(phoenolpyruvate carboxykinase) (85%) and G6pase (glucose-6-phosphatase) (55%) was observed in S rats (P < 0.05).
A 40% decrease in Apob (apolipoprotein B-100) and an increase in hepatic lipids (P < 0.05), together with a double
increase in TNF-α (P < 0.001), were observed in S rats, but without liver histopathological changes. These stress effects
on lipid accumulation and TNF-α were abolished in SF rats (P < 0.05).
Conclusions: Fructose does not enhance stress effects on hepatic lipid and glucose metabolism but attenuates its
effects on hepatic lipid accumulation and inflammation, suggesting that, in female rats, AMPK activation prevails over
stress-induced effects.
PB  - Oxford University Press on behalf of the American Society of Nutrition
T2  - The Journal of Nutrition
T1  - Fructose-Rich Diet Attenuates Stress-Induced Metabolic Disturbances in the Liver of Adult Female Rats
IS  - 12
VL  - 151
DO  - 10.1093/jn/nxab294
SP  - 3661
EP  - 3670
ER  - 

@article{
author = "Kovačević, Sanja and Elaković, Ivana and Vojnović-Milutinović, Danijela and Nikolić-Kokić, Aleksandra and Blagojević, Duško and Matić, Gordana and Tappy, Luc and Đorđević, Ana and Brkljačić, Jelena",
year = "2021",
abstract = "Background: Both fructose consumption and chronic stress contribute to the development of metabolic disorders.
The consequences of such combination are not fully understood.
Objective: We investigated whether fructose supplementation and chronic stress synergistically disturb hepatic lipid
and glucose metabolism. The role of energy sensing, redox, and inflammatory status during development of metabolic
disturbances was investigated.
Methods: Female Wistar rats, aged 2.5 mo, were divided into 4 experimental groups: control (C) fed a standard diet
(commercial food and drinking water); fructose (F) fed the same food and 10% fructose solution; stress (S) fed the
standard diet and subjected to chronic unpredictable stress and, stress + fructose (SF) combining conditions F and
S as above. Stress included daily stressors: cold water forced swimming, physical restraint, cold room, wet bedding,
rocking, switching, or tilting cages. After 9 wk, hepatic enzymes and transcription factors involved in gluconeogenesis,
lipogenesis, fatty acid oxidation, antioxidative defence, energy sensing, and cytokines were assessed by qPCR, Western
blotting, and spectrophotometry and analyzed by 2-factor ANOVA.
Results: Fructose increased AMP-activated protein kinase (AMPK) phosphorylation (40%; P < 0.05) and the ratio of
inhibitory phosphorylation to total acetyl-CoA carboxylase (46%; P < 0.01), and decreased sterol regulatory element
binding protein 1c nuclear translocation by 30% (P < 0.05) in F and SF compared with C rats. Increased phosPck
(phoenolpyruvate carboxykinase) (85%) and G6pase (glucose-6-phosphatase) (55%) was observed in S rats (P < 0.05).
A 40% decrease in Apob (apolipoprotein B-100) and an increase in hepatic lipids (P < 0.05), together with a double
increase in TNF-α (P < 0.001), were observed in S rats, but without liver histopathological changes. These stress effects
on lipid accumulation and TNF-α were abolished in SF rats (P < 0.05).
Conclusions: Fructose does not enhance stress effects on hepatic lipid and glucose metabolism but attenuates its
effects on hepatic lipid accumulation and inflammation, suggesting that, in female rats, AMPK activation prevails over
stress-induced effects.",
publisher = "Oxford University Press on behalf of the American Society of Nutrition",
journal = "The Journal of Nutrition",
title = "Fructose-Rich Diet Attenuates Stress-Induced Metabolic Disturbances in the Liver of Adult Female Rats",
number = "12",
volume = "151",
doi = "10.1093/jn/nxab294",
pages = "3661-3670"
}

Kovačević, S., Elaković, I., Vojnović-Milutinović, D., Nikolić-Kokić, A., Blagojević, D., Matić, G., Tappy, L., Đorđević, A.,& Brkljačić, J.. (2021). Fructose-Rich Diet Attenuates Stress-Induced Metabolic Disturbances in the Liver of Adult Female Rats. in The Journal of Nutrition
Oxford University Press on behalf of the American Society of Nutrition., 151(12), 3661-3670.
https://doi.org/10.1093/jn/nxab294

Kovačević S, Elaković I, Vojnović-Milutinović D, Nikolić-Kokić A, Blagojević D, Matić G, Tappy L, Đorđević A, Brkljačić J. Fructose-Rich Diet Attenuates Stress-Induced Metabolic Disturbances in the Liver of Adult Female Rats. in The Journal of Nutrition. 2021;151(12):3661-3670.
doi:10.1093/jn/nxab294 .

Kovačević, Sanja, Elaković, Ivana, Vojnović-Milutinović, Danijela, Nikolić-Kokić, Aleksandra, Blagojević, Duško, Matić, Gordana, Tappy, Luc, Đorđević, Ana, Brkljačić, Jelena, "Fructose-Rich Diet Attenuates Stress-Induced Metabolic Disturbances in the Liver of Adult Female Rats" in The Journal of Nutrition, 151, no. 12 (2021):3661-3670,
https://doi.org/10.1093/jn/nxab294 . .

TY  - JOUR
AU  - Tatalović, Nikola
AU  - Vidonja Uzelac, Teodora
AU  - Oreščanin Dušić, Zorana
AU  - Nikolić-Kokić, Aleksandra
AU  - Bresjanac, Mara
AU  - Blagojević, Duško
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4662
AB  - Ibogaine effects are mediated by cellular receptors, ATP depletion followed by ROS
production and antioxidant enzyme activity elevation in a dose and time dependent manner. Since
the role of KATP channels and β -adrenoceptors in ROS cellular circuit was established here we
explored their role in ibogaine pro-antioxidant effectiveness. Single dose of ibogaine (10 mg/L i.e.,
28.8 µmol/L) was applied to isolated rat uterus (spontaneous and Ca2+-stimulated) and contractility
and antioxidant enzymes activity were monitored during 4 h. Ibogaine increased amplitude and
frequency of spontaneous active uteri immediately after addition that was prevented by propranolol
( 1 and  2 adrenoceptors selective antagonists) and glibenclamide (KATP sensitive channels inhibitor;
only frequency) pre-treatment. In Ca2+-stimulated uteri, ibogaine decreased both amplitude and
frequency after 4 h. Pre-treatment with propranolol abolished ibogaine induced amplitude lowering,
while glibenclamide had no effect. In both types of active uterus, ibogaine induced a decrease in
SOD1 and an increase in CAT activity after 2 h. In Ca2+-stimulated uterus, there was also a decrease
of SOD2 activity after 2 h. After 4 h, SOD1 activity returned to the baseline level, but GSH-Px activity
increased. Pre-treatment with both propranolol and glibenclamide abolished observed changes of
antioxidant enzymes activity suggesting that ibogaine pro-antioxidative effectiveness is β -adrenergic
receptors and KATP channels mediated.
PB  - Basel: MDPI
T2  - Antioxidants
T1  - Ibogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and KATP Channels Mediated
IS  - 11
VL  - 10
DO  - 10.3390/antiox10111792
SP  - 1792
ER  - 

@article{
author = "Tatalović, Nikola and Vidonja Uzelac, Teodora and Oreščanin Dušić, Zorana and Nikolić-Kokić, Aleksandra and Bresjanac, Mara and Blagojević, Duško",
year = "2021",
abstract = "Ibogaine effects are mediated by cellular receptors, ATP depletion followed by ROS
production and antioxidant enzyme activity elevation in a dose and time dependent manner. Since
the role of KATP channels and β -adrenoceptors in ROS cellular circuit was established here we
explored their role in ibogaine pro-antioxidant effectiveness. Single dose of ibogaine (10 mg/L i.e.,
28.8 µmol/L) was applied to isolated rat uterus (spontaneous and Ca2+-stimulated) and contractility
and antioxidant enzymes activity were monitored during 4 h. Ibogaine increased amplitude and
frequency of spontaneous active uteri immediately after addition that was prevented by propranolol
( 1 and  2 adrenoceptors selective antagonists) and glibenclamide (KATP sensitive channels inhibitor;
only frequency) pre-treatment. In Ca2+-stimulated uteri, ibogaine decreased both amplitude and
frequency after 4 h. Pre-treatment with propranolol abolished ibogaine induced amplitude lowering,
while glibenclamide had no effect. In both types of active uterus, ibogaine induced a decrease in
SOD1 and an increase in CAT activity after 2 h. In Ca2+-stimulated uterus, there was also a decrease
of SOD2 activity after 2 h. After 4 h, SOD1 activity returned to the baseline level, but GSH-Px activity
increased. Pre-treatment with both propranolol and glibenclamide abolished observed changes of
antioxidant enzymes activity suggesting that ibogaine pro-antioxidative effectiveness is β -adrenergic
receptors and KATP channels mediated.",
publisher = "Basel: MDPI",
journal = "Antioxidants",
title = "Ibogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and KATP Channels Mediated",
number = "11",
volume = "10",
doi = "10.3390/antiox10111792",
pages = "1792"
}

Tatalović, N., Vidonja Uzelac, T., Oreščanin Dušić, Z., Nikolić-Kokić, A., Bresjanac, M.,& Blagojević, D.. (2021). Ibogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and KATP Channels Mediated. in Antioxidants
Basel: MDPI., 10(11), 1792.
https://doi.org/10.3390/antiox10111792

Tatalović N, Vidonja Uzelac T, Oreščanin Dušić Z, Nikolić-Kokić A, Bresjanac M, Blagojević D. Ibogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and KATP Channels Mediated. in Antioxidants. 2021;10(11):1792.
doi:10.3390/antiox10111792 .

Tatalović, Nikola, Vidonja Uzelac, Teodora, Oreščanin Dušić, Zorana, Nikolić-Kokić, Aleksandra, Bresjanac, Mara, Blagojević, Duško, "Ibogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and KATP Channels Mediated" in Antioxidants, 10, no. 11 (2021):1792,
https://doi.org/10.3390/antiox10111792 . .

TY  - JOUR
AU  - Tatalović, Nikola
AU  - Vidonja Uzelac, Teodora
AU  - Mijović, Milica
AU  - Koželj, Gordana
AU  - Nikolić-Kokić, Aleksandra
AU  - Oreščanin Dušić, Zorana
AU  - Bresjanac, Mara
AU  - Blagojević, Duško
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4706
AB  - Ibogaine induces rapid changes in cellular energetics followed by the elevation of antioxidant activities. As shown earlier in male rats, ibogaine treatment with both 1 and 20 mg/kg b.w. per os led to significant glycogenolytic activity in the liver. In this work, female rats treated with the same doses of ibogaine per os displayed lower liver glycogenolytic activity relative to males, dilatation of the central vein and branches of the portal vein, and increased concentration of thiols 6 h after treatment. These changes were followed by increased catalase activity and lipid peroxidation, and decreased xanthine oxidase activity after 24 h. In kidneys, mild histopathological changes were found in all treated animals, accompanied by a decrease of glutathione reductase (after 6 and 24 h at both doses) and an increase of catalase (6 h) and xanthine oxidase activity (6 and 24 h). Ibogaine did not affect antioxidant enzymes activity in erythrocytes. Bioavailability of ibogaine was two to three times higher in females than males, with similar kinetic profiles. Compared to previous results in males, ibogaine showed sex specific effect at the level of antioxidant cellular system. Effects of ibogaine in rats are sex- and tissue-specific, and also dose- and time-dependent.
PB  - Basel: MDPI
T2  - Life
T1  - Ibogaine Has Sex-Specific Plasma Bioavailability, Histopathological and Redox/Antioxidant Effects in Rat Liver and Kidneys: A Study on Females
IS  - 1
VL  - 12
DO  - 10.3390/life12010016
SP  - 16
ER  - 

@article{
author = "Tatalović, Nikola and Vidonja Uzelac, Teodora and Mijović, Milica and Koželj, Gordana and Nikolić-Kokić, Aleksandra and Oreščanin Dušić, Zorana and Bresjanac, Mara and Blagojević, Duško",
year = "2021",
abstract = "Ibogaine induces rapid changes in cellular energetics followed by the elevation of antioxidant activities. As shown earlier in male rats, ibogaine treatment with both 1 and 20 mg/kg b.w. per os led to significant glycogenolytic activity in the liver. In this work, female rats treated with the same doses of ibogaine per os displayed lower liver glycogenolytic activity relative to males, dilatation of the central vein and branches of the portal vein, and increased concentration of thiols 6 h after treatment. These changes were followed by increased catalase activity and lipid peroxidation, and decreased xanthine oxidase activity after 24 h. In kidneys, mild histopathological changes were found in all treated animals, accompanied by a decrease of glutathione reductase (after 6 and 24 h at both doses) and an increase of catalase (6 h) and xanthine oxidase activity (6 and 24 h). Ibogaine did not affect antioxidant enzymes activity in erythrocytes. Bioavailability of ibogaine was two to three times higher in females than males, with similar kinetic profiles. Compared to previous results in males, ibogaine showed sex specific effect at the level of antioxidant cellular system. Effects of ibogaine in rats are sex- and tissue-specific, and also dose- and time-dependent.",
publisher = "Basel: MDPI",
journal = "Life",
title = "Ibogaine Has Sex-Specific Plasma Bioavailability, Histopathological and Redox/Antioxidant Effects in Rat Liver and Kidneys: A Study on Females",
number = "1",
volume = "12",
doi = "10.3390/life12010016",
pages = "16"
}

Tatalović, N., Vidonja Uzelac, T., Mijović, M., Koželj, G., Nikolić-Kokić, A., Oreščanin Dušić, Z., Bresjanac, M.,& Blagojević, D.. (2021). Ibogaine Has Sex-Specific Plasma Bioavailability, Histopathological and Redox/Antioxidant Effects in Rat Liver and Kidneys: A Study on Females. in Life
Basel: MDPI., 12(1), 16.
https://doi.org/10.3390/life12010016

Tatalović N, Vidonja Uzelac T, Mijović M, Koželj G, Nikolić-Kokić A, Oreščanin Dušić Z, Bresjanac M, Blagojević D. Ibogaine Has Sex-Specific Plasma Bioavailability, Histopathological and Redox/Antioxidant Effects in Rat Liver and Kidneys: A Study on Females. in Life. 2021;12(1):16.
doi:10.3390/life12010016 .

Tatalović, Nikola, Vidonja Uzelac, Teodora, Mijović, Milica, Koželj, Gordana, Nikolić-Kokić, Aleksandra, Oreščanin Dušić, Zorana, Bresjanac, Mara, Blagojević, Duško, "Ibogaine Has Sex-Specific Plasma Bioavailability, Histopathological and Redox/Antioxidant Effects in Rat Liver and Kidneys: A Study on Females" in Life, 12, no. 1 (2021):16,
https://doi.org/10.3390/life12010016 . .

TY  - JOUR
AU  - Elaković, Ivana
AU  - Kovačević, Sanja
AU  - Vojnović-Milutinović, Danijela
AU  - Nikolić-Kokić, Aleksandra
AU  - Glban, Alhadi M.
AU  - Spasić, Mihajlo
AU  - Tappy, Luc
AU  - Đorđević, Ana
AU  - Matić, Gordana
AU  - Brkljačić, Jelena
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3983
AB  - The effects of early-life fructose consumption on hepatic signaling pathways and their relation to the development of metabolic disorders in later life are not fully understood. To investigate whether fructose over consumption at a young age induces alterations in glucocorticoid signaling that  might  contribute  to  development  of  metabolic  disturbances,  we  analysed  glucocorticoid receptor hormone-binding parameters and expression of its target genes involved in gluconeogenesis (phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) and lipid metabolism (lipin-1),as well as redox and inflammatory status in the liver of female rats subjected to a fructose-rich diet immediately after weaning.  The fructose diet increased hepatic corticosterone concentration,11β-hydroxysteroid  dehydrogenase  type  1  level,   glucocorticoid  receptor  protein  level  and hormone-binding activity, as well as lipin-1 level. The expression of glucose-6-phosphatase was reduced  in  fructose-fed  rats,  while  phosphoenolpyruvate  carboxykinase  remained  unaltered.The  fructose-rich  diet  increased  the  level  of  fructose  transporter  GLUT2,  while  the  expression of  fructolytic  enzymes  fructokinase  and  aldolase  B  remained  unaltered.   The  diet  also  affected pro-inflammatory pathways, but had no effect on the antioxidant defence system.  In conclusion, a fructose-rich diet applied immediately after weaning promoted lipogenesis and enhanced hepatic glucocorticoid signaling, possibly to protect against inflammatory damage, but without an effect on gluconeogenesis and antioxidant enzymes. Yet, prolonged treatment might ultimately lead to more pronounced metabolic disturbances.
PB  - Basel, Switzerland : Multidisciplinary Digital Publishing Institute (MDPI)
T2  - Nutrients
T1  - Fructose Consumption Affects Glucocorticoid Signaling in the Liver of Young Female Rats
IS  - 11
VL  - 12
DO  - 10.3390/nu12113470
SP  - 3470
ER  - 

@article{
author = "Elaković, Ivana and Kovačević, Sanja and Vojnović-Milutinović, Danijela and Nikolić-Kokić, Aleksandra and Glban, Alhadi M. and Spasić, Mihajlo and Tappy, Luc and Đorđević, Ana and Matić, Gordana and Brkljačić, Jelena",
year = "2020",
abstract = "The effects of early-life fructose consumption on hepatic signaling pathways and their relation to the development of metabolic disorders in later life are not fully understood. To investigate whether fructose over consumption at a young age induces alterations in glucocorticoid signaling that  might  contribute  to  development  of  metabolic  disturbances,  we  analysed  glucocorticoid receptor hormone-binding parameters and expression of its target genes involved in gluconeogenesis (phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) and lipid metabolism (lipin-1),as well as redox and inflammatory status in the liver of female rats subjected to a fructose-rich diet immediately after weaning.  The fructose diet increased hepatic corticosterone concentration,11β-hydroxysteroid  dehydrogenase  type  1  level,   glucocorticoid  receptor  protein  level  and hormone-binding activity, as well as lipin-1 level. The expression of glucose-6-phosphatase was reduced  in  fructose-fed  rats,  while  phosphoenolpyruvate  carboxykinase  remained  unaltered.The  fructose-rich  diet  increased  the  level  of  fructose  transporter  GLUT2,  while  the  expression of  fructolytic  enzymes  fructokinase  and  aldolase  B  remained  unaltered.   The  diet  also  affected pro-inflammatory pathways, but had no effect on the antioxidant defence system.  In conclusion, a fructose-rich diet applied immediately after weaning promoted lipogenesis and enhanced hepatic glucocorticoid signaling, possibly to protect against inflammatory damage, but without an effect on gluconeogenesis and antioxidant enzymes. Yet, prolonged treatment might ultimately lead to more pronounced metabolic disturbances.",
publisher = "Basel, Switzerland : Multidisciplinary Digital Publishing Institute (MDPI)",
journal = "Nutrients",
title = "Fructose Consumption Affects Glucocorticoid Signaling in the Liver of Young Female Rats",
number = "11",
volume = "12",
doi = "10.3390/nu12113470",
pages = "3470"
}

Elaković, I., Kovačević, S., Vojnović-Milutinović, D., Nikolić-Kokić, A., Glban, A. M., Spasić, M., Tappy, L., Đorđević, A., Matić, G.,& Brkljačić, J.. (2020). Fructose Consumption Affects Glucocorticoid Signaling in the Liver of Young Female Rats. in Nutrients
Basel, Switzerland : Multidisciplinary Digital Publishing Institute (MDPI)., 12(11), 3470.
https://doi.org/10.3390/nu12113470

Elaković I, Kovačević S, Vojnović-Milutinović D, Nikolić-Kokić A, Glban AM, Spasić M, Tappy L, Đorđević A, Matić G, Brkljačić J. Fructose Consumption Affects Glucocorticoid Signaling in the Liver of Young Female Rats. in Nutrients. 2020;12(11):3470.
doi:10.3390/nu12113470 .

Elaković, Ivana, Kovačević, Sanja, Vojnović-Milutinović, Danijela, Nikolić-Kokić, Aleksandra, Glban, Alhadi M., Spasić, Mihajlo, Tappy, Luc, Đorđević, Ana, Matić, Gordana, Brkljačić, Jelena, "Fructose Consumption Affects Glucocorticoid Signaling in the Liver of Young Female Rats" in Nutrients, 12, no. 11 (2020):3470,
https://doi.org/10.3390/nu12113470 . .

TY  - JOUR
AU  - Spasić, Snežana
AU  - Nikolić-Kokić, Aleksandra
AU  - Miletić, Srđan
AU  - Oreščanin Dušić, Zorana
AU  - Spasić, Mihajlo
AU  - Blagojević, Duško
AU  - Stević, Zorica
PY  - 2020
UR  - https://www.eurekaselect.com/179582/article
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32077821
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3757
AB  - Radicava™ (Edaravone) was approved the Food and Drug Administration (FDA) as a new treatment for amyotrophic lateral sclerosis (ALS). Edaravone is a synthetic antioxidant that specifically targets oxidative damage interacting with lipid radicals in the cell. In ALS disease the multiple cell types are involved in devastating loss of motor neurons. Mutations and biochemical changes in various cell types jointly contribute to motor neuron death, disease onset, and disease progression. The overall mechanism of neurodegeneration in ALS is still not completely understood. Dying motor neurons have been reported to exhibit features of apoptosis. However, non-apoptotic features of dying motor neurons have also been reported such as ferroptosis. The role of Edaravone in the prevention of ferroptosis in parallel with other therapeutic approaches to ALS therapy is discussed.
PB  - Bentham Science Publishers Ltd.
T2  - Current Drug Targets
T1  - Edaravone May Prevent Ferroptosis in ALS.
IS  - 8
VL  - 21
DO  - 10.2174/1389450121666200220123305
SP  - 776
EP  - 780
ER  - 

@article{
author = "Spasić, Snežana and Nikolić-Kokić, Aleksandra and Miletić, Srđan and Oreščanin Dušić, Zorana and Spasić, Mihajlo and Blagojević, Duško and Stević, Zorica",
year = "2020",
abstract = "Radicava™ (Edaravone) was approved the Food and Drug Administration (FDA) as a new treatment for amyotrophic lateral sclerosis (ALS). Edaravone is a synthetic antioxidant that specifically targets oxidative damage interacting with lipid radicals in the cell. In ALS disease the multiple cell types are involved in devastating loss of motor neurons. Mutations and biochemical changes in various cell types jointly contribute to motor neuron death, disease onset, and disease progression. The overall mechanism of neurodegeneration in ALS is still not completely understood. Dying motor neurons have been reported to exhibit features of apoptosis. However, non-apoptotic features of dying motor neurons have also been reported such as ferroptosis. The role of Edaravone in the prevention of ferroptosis in parallel with other therapeutic approaches to ALS therapy is discussed.",
publisher = "Bentham Science Publishers Ltd.",
journal = "Current Drug Targets",
title = "Edaravone May Prevent Ferroptosis in ALS.",
number = "8",
volume = "21",
doi = "10.2174/1389450121666200220123305",
pages = "776-780"
}

Spasić, S., Nikolić-Kokić, A., Miletić, S., Oreščanin Dušić, Z., Spasić, M., Blagojević, D.,& Stević, Z.. (2020). Edaravone May Prevent Ferroptosis in ALS.. in Current Drug Targets
Bentham Science Publishers Ltd.., 21(8), 776-780.
https://doi.org/10.2174/1389450121666200220123305

Spasić S, Nikolić-Kokić A, Miletić S, Oreščanin Dušić Z, Spasić M, Blagojević D, Stević Z. Edaravone May Prevent Ferroptosis in ALS.. in Current Drug Targets. 2020;21(8):776-780.
doi:10.2174/1389450121666200220123305 .

Spasić, Snežana, Nikolić-Kokić, Aleksandra, Miletić, Srđan, Oreščanin Dušić, Zorana, Spasić, Mihajlo, Blagojević, Duško, Stević, Zorica, "Edaravone May Prevent Ferroptosis in ALS." in Current Drug Targets, 21, no. 8 (2020):776-780,
https://doi.org/10.2174/1389450121666200220123305 . .

TY  - CONF
AU  - Blagojević, Duško
AU  - Nikolić-Kokić, Aleksandra
AU  - Tatalović, Nikola
AU  - Oreščanin Dušić, Zorana
AU  - Vidonja Uzelac, Teodora
AU  - Spasić, Mihajlo
AU  - Miljević, Čedo
PY  - 2019
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4278
AB  - Different studies reported that patients with schizophrenia had lower cholesterol levels in blood compared to healthy controls. However, it is unclear whether changed cholesterol concentration and lipid status are a consequence of changed neurotransmitter metabolism intrinsic to origin of the disease or affect central nervous system neurotransmission and influence the development of psychiatric disorders. Anyway, schizophrenia treatment with atypical antipsychotic drugs (APD) additionally influences lipid status in blood and all families of APD agents can cause severe side effects including dyslipidemia. Therefore, the aim of the present study was to evaluate effects of 28-day treatment with recommended human daily dose of APD: ziprasidone, clozapine, sertindole on 3 months old healthy male rats’ levels of cholesterol, HDL, LDL, and triglyceride in the blood serum. Our results showed a decrease of both triglycerides and cholesterol in clozapine treated rats. In ziprasidone treated rats triglycerides and HDL were lower comparing to untreated controls. Treatment with sertindole had no effects on lipid blood serum levels. However, there were no changes of index of atherosclerosis in APD treated rats. Our results showed that treatment with clozapine and ziprasidone influence blood serum levels of lipids indicating altered lipid metabolism.
PB  - Bologna: Federation of European Physiological Societies
C3  - Joint Meeting of the Federation of European Physiological Societies (FEPS) and the Italian Physiological Society (SIF); 2019 Sep 10-13; Bologna, Italy
T1  - The effects of clozapine, ziprasidone and sertindole treatment on lipid profile in rats
IS  - Supplement 718
VL  - 227
DO  - 10.1111/apha.13366
SP  - 85
EP  - 85
ER  - 

@conference{
author = "Blagojević, Duško and Nikolić-Kokić, Aleksandra and Tatalović, Nikola and Oreščanin Dušić, Zorana and Vidonja Uzelac, Teodora and Spasić, Mihajlo and Miljević, Čedo",
year = "2019",
abstract = "Different studies reported that patients with schizophrenia had lower cholesterol levels in blood compared to healthy controls. However, it is unclear whether changed cholesterol concentration and lipid status are a consequence of changed neurotransmitter metabolism intrinsic to origin of the disease or affect central nervous system neurotransmission and influence the development of psychiatric disorders. Anyway, schizophrenia treatment with atypical antipsychotic drugs (APD) additionally influences lipid status in blood and all families of APD agents can cause severe side effects including dyslipidemia. Therefore, the aim of the present study was to evaluate effects of 28-day treatment with recommended human daily dose of APD: ziprasidone, clozapine, sertindole on 3 months old healthy male rats’ levels of cholesterol, HDL, LDL, and triglyceride in the blood serum. Our results showed a decrease of both triglycerides and cholesterol in clozapine treated rats. In ziprasidone treated rats triglycerides and HDL were lower comparing to untreated controls. Treatment with sertindole had no effects on lipid blood serum levels. However, there were no changes of index of atherosclerosis in APD treated rats. Our results showed that treatment with clozapine and ziprasidone influence blood serum levels of lipids indicating altered lipid metabolism.",
publisher = "Bologna: Federation of European Physiological Societies",
journal = "Joint Meeting of the Federation of European Physiological Societies (FEPS) and the Italian Physiological Society (SIF); 2019 Sep 10-13; Bologna, Italy",
title = "The effects of clozapine, ziprasidone and sertindole treatment on lipid profile in rats",
number = "Supplement 718",
volume = "227",
doi = "10.1111/apha.13366",
pages = "85-85"
}

Blagojević, D., Nikolić-Kokić, A., Tatalović, N., Oreščanin Dušić, Z., Vidonja Uzelac, T., Spasić, M.,& Miljević, Č.. (2019). The effects of clozapine, ziprasidone and sertindole treatment on lipid profile in rats. in Joint Meeting of the Federation of European Physiological Societies (FEPS) and the Italian Physiological Society (SIF); 2019 Sep 10-13; Bologna, Italy
Bologna: Federation of European Physiological Societies., 227(Supplement 718), 85-85.
https://doi.org/10.1111/apha.13366

Blagojević D, Nikolić-Kokić A, Tatalović N, Oreščanin Dušić Z, Vidonja Uzelac T, Spasić M, Miljević Č. The effects of clozapine, ziprasidone and sertindole treatment on lipid profile in rats. in Joint Meeting of the Federation of European Physiological Societies (FEPS) and the Italian Physiological Society (SIF); 2019 Sep 10-13; Bologna, Italy. 2019;227(Supplement 718):85-85.
doi:10.1111/apha.13366 .

Blagojević, Duško, Nikolić-Kokić, Aleksandra, Tatalović, Nikola, Oreščanin Dušić, Zorana, Vidonja Uzelac, Teodora, Spasić, Mihajlo, Miljević, Čedo, "The effects of clozapine, ziprasidone and sertindole treatment on lipid profile in rats" in Joint Meeting of the Federation of European Physiological Societies (FEPS) and the Italian Physiological Society (SIF); 2019 Sep 10-13; Bologna, Italy, 227, no. Supplement 718 (2019):85-85,
https://doi.org/10.1111/apha.13366 . .

TY  - JOUR
AU  - Vidonja Uzelac, Teodora
AU  - Tatalović, Nikola
AU  - Mijović, Milica
AU  - Nikolić-Kokić, Aleksandra
AU  - Oreščanin Dušić, Zorana
AU  - Bresjanac, Mara
AU  - Blagojević, Duško
PY  - 2019
UR  - http://www.doiserbia.nb.rs/Article.aspx?ID=0354-46641900006V
UR  - http://www.serbiosoc.org.rs/arch/index.php/abs/article/view/3984
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3395
AB  - Our previous results showed that a single oral dose (1 or 20 mg/kg body weight) of the anti-addiction agent ibogaine induced in rats 6 and 24 h after administration glycogenolytic activity in hepatocytes, followed by a mild oxidative stress. In this work, we examined the in vivo effect of the same doses of ibogaine on rat kidney morphology, antioxidant enzyme (superoxide dismutases (SOD1 and 2), catalase, glutathione peroxidase, glutathione reductase (GR) and glutathione- S-transferase) activities, and oxidative stress (TBARS) and redox (-SH groups) parameters. The dose of 1 mg/kg ibogaine induced an elevation in SOD1 activity and decreased GR activity after 6 and 24 h. GR activity was decreased at 6 and 24 h after 20 mg/kg ibogaine administration, suggesting changed redox homeostasis. After 24 h, we observed an increase in moderate morphological changes, without changes in urinalyses, indicating that kidney function was not measurably affected. Nevertheless, kidney-function monitoring during and following ibogaine use in human subjects is advisable.
T2  - Archives of Biological Sciences
T1  - Effects of ibogaine per os treatment on redox homeostasis in rat kidney
IS  - 2
VL  - 71
DO  - 10.2298/ABS190208006V
SP  - 245
EP  - 252
ER  - 

@article{
author = "Vidonja Uzelac, Teodora and Tatalović, Nikola and Mijović, Milica and Nikolić-Kokić, Aleksandra and Oreščanin Dušić, Zorana and Bresjanac, Mara and Blagojević, Duško",
year = "2019",
abstract = "Our previous results showed that a single oral dose (1 or 20 mg/kg body weight) of the anti-addiction agent ibogaine induced in rats 6 and 24 h after administration glycogenolytic activity in hepatocytes, followed by a mild oxidative stress. In this work, we examined the in vivo effect of the same doses of ibogaine on rat kidney morphology, antioxidant enzyme (superoxide dismutases (SOD1 and 2), catalase, glutathione peroxidase, glutathione reductase (GR) and glutathione- S-transferase) activities, and oxidative stress (TBARS) and redox (-SH groups) parameters. The dose of 1 mg/kg ibogaine induced an elevation in SOD1 activity and decreased GR activity after 6 and 24 h. GR activity was decreased at 6 and 24 h after 20 mg/kg ibogaine administration, suggesting changed redox homeostasis. After 24 h, we observed an increase in moderate morphological changes, without changes in urinalyses, indicating that kidney function was not measurably affected. Nevertheless, kidney-function monitoring during and following ibogaine use in human subjects is advisable.",
journal = "Archives of Biological Sciences",
title = "Effects of ibogaine per os treatment on redox homeostasis in rat kidney",
number = "2",
volume = "71",
doi = "10.2298/ABS190208006V",
pages = "245-252"
}

Vidonja Uzelac, T., Tatalović, N., Mijović, M., Nikolić-Kokić, A., Oreščanin Dušić, Z., Bresjanac, M.,& Blagojević, D.. (2019). Effects of ibogaine per os treatment on redox homeostasis in rat kidney. in Archives of Biological Sciences, 71(2), 245-252.
https://doi.org/10.2298/ABS190208006V

Vidonja Uzelac T, Tatalović N, Mijović M, Nikolić-Kokić A, Oreščanin Dušić Z, Bresjanac M, Blagojević D. Effects of ibogaine per os treatment on redox homeostasis in rat kidney. in Archives of Biological Sciences. 2019;71(2):245-252.
doi:10.2298/ABS190208006V .

Vidonja Uzelac, Teodora, Tatalović, Nikola, Mijović, Milica, Nikolić-Kokić, Aleksandra, Oreščanin Dušić, Zorana, Bresjanac, Mara, Blagojević, Duško, "Effects of ibogaine per os treatment on redox homeostasis in rat kidney" in Archives of Biological Sciences, 71, no. 2 (2019):245-252,
https://doi.org/10.2298/ABS190208006V . .

TY  - JOUR
AU  - Davidović-Plavšić, Biljana
AU  - Lukić, Nataša
AU  - Nikolić-Kokić, Aleksandra
AU  - Kukavica, Biljana
PY  - 2019
UR  - http://www.doiserbia.nb.rs/Article.aspx?ID=0352-51391800115D
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3396
AB  - The aim of this work was to investigate the effect of the commercial formulation hemazin SC 500, an herbicide containing terbuthylazine as the active compound, on the isoenzyme patterns and activities of Cu-Zn superoxide dismutase (SOD1) and catalase (CAT), as well as on the glutathione S-transferase (GST) activity, in human erythrocytes in vitro. The human erythrocytes were treated with hemazin SC 500 over a broad range of terbuthylazine concentrations (37 nmol L-1– –37 mol L-1) for 1 and 3 h at a temperature of 37°C. Native electrophoresis of the control and treated samples revealed two SOD1 and one CAT isoform. Treatment did not affect the SOD1 and CAT isoenzyme profile, but induced a change in their activities. Terbuthylazine at lower concentration induced a significant increase of the total SOD1 activity and decreased the GST activity in samples incubated for 1 and 3 h. On the other hand, the highest increase in the CAT activity was observed for the sample treated for 1 h with a higher concentration of terbuthylazine. Hemazin SC 500 containing terbuthylazine induces changes in the erythrocyte antioxidative system whereby the response of individual enzymatic antioxidants depends on the concentration of the pesticide and the incubation time.
T2  - Journal of the Serbian Chemical Society
T1  - Effects of hemazin SC 500 (terbuthylazine) on antioxidative enzymes in human erythrocytes in vitro
IS  - 5
VL  - 84
DO  - 10.2298/JSC181011115D
SP  - 455
EP  - 465
ER  - 

@article{
author = "Davidović-Plavšić, Biljana and Lukić, Nataša and Nikolić-Kokić, Aleksandra and Kukavica, Biljana",
year = "2019",
abstract = "The aim of this work was to investigate the effect of the commercial formulation hemazin SC 500, an herbicide containing terbuthylazine as the active compound, on the isoenzyme patterns and activities of Cu-Zn superoxide dismutase (SOD1) and catalase (CAT), as well as on the glutathione S-transferase (GST) activity, in human erythrocytes in vitro. The human erythrocytes were treated with hemazin SC 500 over a broad range of terbuthylazine concentrations (37 nmol L-1– –37 mol L-1) for 1 and 3 h at a temperature of 37°C. Native electrophoresis of the control and treated samples revealed two SOD1 and one CAT isoform. Treatment did not affect the SOD1 and CAT isoenzyme profile, but induced a change in their activities. Terbuthylazine at lower concentration induced a significant increase of the total SOD1 activity and decreased the GST activity in samples incubated for 1 and 3 h. On the other hand, the highest increase in the CAT activity was observed for the sample treated for 1 h with a higher concentration of terbuthylazine. Hemazin SC 500 containing terbuthylazine induces changes in the erythrocyte antioxidative system whereby the response of individual enzymatic antioxidants depends on the concentration of the pesticide and the incubation time.",
journal = "Journal of the Serbian Chemical Society",
title = "Effects of hemazin SC 500 (terbuthylazine) on antioxidative enzymes in human erythrocytes in vitro",
number = "5",
volume = "84",
doi = "10.2298/JSC181011115D",
pages = "455-465"
}

Davidović-Plavšić, B., Lukić, N., Nikolić-Kokić, A.,& Kukavica, B.. (2019). Effects of hemazin SC 500 (terbuthylazine) on antioxidative enzymes in human erythrocytes in vitro. in Journal of the Serbian Chemical Society, 84(5), 455-465.
https://doi.org/10.2298/JSC181011115D

Davidović-Plavšić B, Lukić N, Nikolić-Kokić A, Kukavica B. Effects of hemazin SC 500 (terbuthylazine) on antioxidative enzymes in human erythrocytes in vitro. in Journal of the Serbian Chemical Society. 2019;84(5):455-465.
doi:10.2298/JSC181011115D .

Davidović-Plavšić, Biljana, Lukić, Nataša, Nikolić-Kokić, Aleksandra, Kukavica, Biljana, "Effects of hemazin SC 500 (terbuthylazine) on antioxidative enzymes in human erythrocytes in vitro" in Journal of the Serbian Chemical Society, 84, no. 5 (2019):455-465,
https://doi.org/10.2298/JSC181011115D . .

TY  - JOUR
AU  - Uzelac, Tamara N.
AU  - Nikolić-Kokić, Aleksandra
AU  - Spasić, Snežana D.
AU  - Mačvanin, Mirjana T.
AU  - Nikolić, Milan R.
AU  - Mandić, Ljuba M.
AU  - Jovanović, Vesna B.
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0009279719310257?via%3Dihub
UR  - http://www.ncbi.nlm.nih.gov/pubmed/31400341
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3454
AB  - Antipsychotic drugs interfere with the antioxidant defense system provoking complex and often toxicological effects. Here we examined differences in plasma albumin reduced free thiol (SH) group content and its reactivity as a consequence of clozapine (CLZ) and ziprasidone (ZIP) binding. Chronic administration of CLZ reduced, whereas treatment with ZIP increased albumin-SH content in rats. Regardless of the ratio of stearic acid (SA) bound to protein, in vitro binding of ZIP to human serum albumin (HSA) increased both the SH group level and reactivity. In contrast, the effect of CLZ on HSA-SH reactivity was dependent on HSA to SA molar ratio. CLZ binding was accompanied by an increase in HSA-SH reactivity in samples with normal, but a reduction of its reactivity level with higher SA/HSA ratio, compared to drug-free samples. We demonstrate by steady-state fluorescence quenching studies that an increase in SA binding to HSA is associated with a significant reduction of binding constant for both antipsychotics. In addition, this is the first report of quantitative characterization of ZIP binding to HSA. Our findings suggest that albumin-SH content and reactivity is modulated by ZIP towards an increased antioxidant defense capacity in circulation, as opposed to CLZ, which can contribute to the safer, more effective treatment of schizophrenia.
T2  - Chemico-Biological Interactions
T1  - Opposite clozapine and ziprasidone effects on the reactivity of plasma albumin SH-group are the consequence of their different binding properties dependent on protein fatty acids content.
VL  - 311
DO  - 10.1016/j.cbi.2019.108787
SP  - 108787
ER  - 

@article{
author = "Uzelac, Tamara N. and Nikolić-Kokić, Aleksandra and Spasić, Snežana D. and Mačvanin, Mirjana T. and Nikolić, Milan R. and Mandić, Ljuba M. and Jovanović, Vesna B.",
year = "2019",
abstract = "Antipsychotic drugs interfere with the antioxidant defense system provoking complex and often toxicological effects. Here we examined differences in plasma albumin reduced free thiol (SH) group content and its reactivity as a consequence of clozapine (CLZ) and ziprasidone (ZIP) binding. Chronic administration of CLZ reduced, whereas treatment with ZIP increased albumin-SH content in rats. Regardless of the ratio of stearic acid (SA) bound to protein, in vitro binding of ZIP to human serum albumin (HSA) increased both the SH group level and reactivity. In contrast, the effect of CLZ on HSA-SH reactivity was dependent on HSA to SA molar ratio. CLZ binding was accompanied by an increase in HSA-SH reactivity in samples with normal, but a reduction of its reactivity level with higher SA/HSA ratio, compared to drug-free samples. We demonstrate by steady-state fluorescence quenching studies that an increase in SA binding to HSA is associated with a significant reduction of binding constant for both antipsychotics. In addition, this is the first report of quantitative characterization of ZIP binding to HSA. Our findings suggest that albumin-SH content and reactivity is modulated by ZIP towards an increased antioxidant defense capacity in circulation, as opposed to CLZ, which can contribute to the safer, more effective treatment of schizophrenia.",
journal = "Chemico-Biological Interactions",
title = "Opposite clozapine and ziprasidone effects on the reactivity of plasma albumin SH-group are the consequence of their different binding properties dependent on protein fatty acids content.",
volume = "311",
doi = "10.1016/j.cbi.2019.108787",
pages = "108787"
}

Uzelac, T. N., Nikolić-Kokić, A., Spasić, S. D., Mačvanin, M. T., Nikolić, M. R., Mandić, L. M.,& Jovanović, V. B.. (2019). Opposite clozapine and ziprasidone effects on the reactivity of plasma albumin SH-group are the consequence of their different binding properties dependent on protein fatty acids content.. in Chemico-Biological Interactions, 311, 108787.
https://doi.org/10.1016/j.cbi.2019.108787

Uzelac TN, Nikolić-Kokić A, Spasić SD, Mačvanin MT, Nikolić MR, Mandić LM, Jovanović VB. Opposite clozapine and ziprasidone effects on the reactivity of plasma albumin SH-group are the consequence of their different binding properties dependent on protein fatty acids content.. in Chemico-Biological Interactions. 2019;311:108787.
doi:10.1016/j.cbi.2019.108787 .

Uzelac, Tamara N., Nikolić-Kokić, Aleksandra, Spasić, Snežana D., Mačvanin, Mirjana T., Nikolić, Milan R., Mandić, Ljuba M., Jovanović, Vesna B., "Opposite clozapine and ziprasidone effects on the reactivity of plasma albumin SH-group are the consequence of their different binding properties dependent on protein fatty acids content." in Chemico-Biological Interactions, 311 (2019):108787,
https://doi.org/10.1016/j.cbi.2019.108787 . .

TY  - CONF
AU  - Tatalović, Nikola
AU  - Vidonja Uzelac, Teodora
AU  - Oreščanin Dušić, Zorana
AU  - Nikolić-Kokić, Aleksandra
AU  - Spasić, Mihajlo
AU  - Blagojević, Duško
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S2451830119319119?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/123456789/3898
AB  - Ibogaine is the main alkaloid in the root bark of Tabernanthe iboga plant which groves in Western-Central Africa. It has been used by natives to overcome fatigue, hunger and thirst, and in higher doses to provoke hallucinations. In the “ibogaine medical subculture” in Europe and America it is used to facilitate abstinence from variety of addictive substances (cocaine, heroin, methadone, alcohol…). It was hypothesized that adaptive changes in ATP-related cell energy homeostasis are important contributing factor, to ibogaine’s anti-addictive activity. Examinations on different experimental models showed that ibogaine caused rapid depletion of ATP accompanied by increased production of reactive oxygen species and the activation of antioxidative enzymes, as well as upregulation of energy related enzymes. Our goal was to investigate the effects of ibogaine oral application on redox balance in rat brain and energy metabolism in liver. The later was estimated by accessing amount of glycogen reserves. The null hypothesis was that ibogaine had no effect on the activity of antioxidative enzymes, concentration of lipid peroxides and free sulfhydryl groups in rat brain, or on the amount of glycogen in liver. In this study 3-month-old female Wistar rats were treated with a single dose 20 mg/kg body weight of ibogaine via gavage. Rats were sacrificed 6 or 24 h after treatment; brain and perfunded liver samples were homogenised and sonicated. Liver sample was also prepared for histological analysis. We measured the activities of antioxidative enzymes, namely total superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and the activity of glutathione S-transferases (GSTs) a xenobiotic detoxification enzyme family member. Concentrations of thiobarbituric acid reactive substances (TBARS) and protein and nonprotein free sulfhydryl groups (–SH) were measured in brain sonicates. Amount of glycogen in liver was determined based on PAS staining. Results were analysed by One-way ANOVA with Tukey's HSD post hoc test, p<0.05. There were no significant changes of measured antioxidative enzymes activity in brain neither 6 nor 24 h after treatment with ibogaine. Also, total activity of GSTs remained unaltered. On the other hand, concentration of TBARS was significantly increased 6 h after treatment while after 24 h TBARS concentration was the same as in controls. Treatment with ibogaine caused an increase of protein free –SH groups concentration which was more pronounced after 24 h. However, the concentration of nonprotein free –SH groups was decreased in brain of treated rats but also more prominently after 24 h. Histological analysis of liver showed that amount of glycogen was decreased in treated rats. Glycogen depletion in the liver of treated rats was greater in 6 h group compared to 24 h group. Increased concentrations of TBARS suggest increased lipid in brain of treated rats. Decreased concentration of nonprotein free –SH groups suggests decreased concentration of reduced glutathione, the main source of nonprotein –SH groups in cells. These findings coincide with ibogaine-induced transient burst in cellular respiration followed by intensive production of reactive oxygen species, described in literature. Despite these indicators of oxidative stress there is no change in the activity of any antioxidative enzyme, not even after 6 h. Unaltered activity of GSTs suggest that applied dose of ibogaine doesn’t have an acute toxic effect on brain. Finally, alterations in glycogen amount in hepatocytes suggest a transient depletion of energy reserves, which are on their way to recovery already 24 h after treatment. All of the aforementioned suggest that after oral administration of ibogaine there is rapid transient changes in redox and energetic homeostasis in brain similar to those described on other experimental models. It seems that antioxidative defense system is capable to preserve redox homeostasis within first 6 h, but some consequences in the form of oxidative damage are still present. Since these are all energy-intensive processes, required energy may have been obtained at the expense of liver glycogen. Having in mind a proposed role of energetic and redox related changes in anti-addictive effects of ibogaine, it is essential to investigate redox balance and energy metabolism in brain within the first hours after ibogaine application.
PB  - Elsevier Ltd.
C3  - IBRO Reports
T1  - Effects of ibogaine treatment on redox homeostasis and energy metabolism in rat
IS  - Supplement
VL  - 7
DO  - 10.1016/j.ibror.2019.09.087
SP  - S43
ER  - 

@conference{
author = "Tatalović, Nikola and Vidonja Uzelac, Teodora and Oreščanin Dušić, Zorana and Nikolić-Kokić, Aleksandra and Spasić, Mihajlo and Blagojević, Duško",
year = "2019",
abstract = "Ibogaine is the main alkaloid in the root bark of Tabernanthe iboga plant which groves in Western-Central Africa. It has been used by natives to overcome fatigue, hunger and thirst, and in higher doses to provoke hallucinations. In the “ibogaine medical subculture” in Europe and America it is used to facilitate abstinence from variety of addictive substances (cocaine, heroin, methadone, alcohol…). It was hypothesized that adaptive changes in ATP-related cell energy homeostasis are important contributing factor, to ibogaine’s anti-addictive activity. Examinations on different experimental models showed that ibogaine caused rapid depletion of ATP accompanied by increased production of reactive oxygen species and the activation of antioxidative enzymes, as well as upregulation of energy related enzymes. Our goal was to investigate the effects of ibogaine oral application on redox balance in rat brain and energy metabolism in liver. The later was estimated by accessing amount of glycogen reserves. The null hypothesis was that ibogaine had no effect on the activity of antioxidative enzymes, concentration of lipid peroxides and free sulfhydryl groups in rat brain, or on the amount of glycogen in liver. In this study 3-month-old female Wistar rats were treated with a single dose 20 mg/kg body weight of ibogaine via gavage. Rats were sacrificed 6 or 24 h after treatment; brain and perfunded liver samples were homogenised and sonicated. Liver sample was also prepared for histological analysis. We measured the activities of antioxidative enzymes, namely total superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and the activity of glutathione S-transferases (GSTs) a xenobiotic detoxification enzyme family member. Concentrations of thiobarbituric acid reactive substances (TBARS) and protein and nonprotein free sulfhydryl groups (–SH) were measured in brain sonicates. Amount of glycogen in liver was determined based on PAS staining. Results were analysed by One-way ANOVA with Tukey's HSD post hoc test, p<0.05. There were no significant changes of measured antioxidative enzymes activity in brain neither 6 nor 24 h after treatment with ibogaine. Also, total activity of GSTs remained unaltered. On the other hand, concentration of TBARS was significantly increased 6 h after treatment while after 24 h TBARS concentration was the same as in controls. Treatment with ibogaine caused an increase of protein free –SH groups concentration which was more pronounced after 24 h. However, the concentration of nonprotein free –SH groups was decreased in brain of treated rats but also more prominently after 24 h. Histological analysis of liver showed that amount of glycogen was decreased in treated rats. Glycogen depletion in the liver of treated rats was greater in 6 h group compared to 24 h group. Increased concentrations of TBARS suggest increased lipid in brain of treated rats. Decreased concentration of nonprotein free –SH groups suggests decreased concentration of reduced glutathione, the main source of nonprotein –SH groups in cells. These findings coincide with ibogaine-induced transient burst in cellular respiration followed by intensive production of reactive oxygen species, described in literature. Despite these indicators of oxidative stress there is no change in the activity of any antioxidative enzyme, not even after 6 h. Unaltered activity of GSTs suggest that applied dose of ibogaine doesn’t have an acute toxic effect on brain. Finally, alterations in glycogen amount in hepatocytes suggest a transient depletion of energy reserves, which are on their way to recovery already 24 h after treatment. All of the aforementioned suggest that after oral administration of ibogaine there is rapid transient changes in redox and energetic homeostasis in brain similar to those described on other experimental models. It seems that antioxidative defense system is capable to preserve redox homeostasis within first 6 h, but some consequences in the form of oxidative damage are still present. Since these are all energy-intensive processes, required energy may have been obtained at the expense of liver glycogen. Having in mind a proposed role of energetic and redox related changes in anti-addictive effects of ibogaine, it is essential to investigate redox balance and energy metabolism in brain within the first hours after ibogaine application.",
publisher = "Elsevier Ltd.",
journal = "IBRO Reports",
title = "Effects of ibogaine treatment on redox homeostasis and energy metabolism in rat",
number = "Supplement",
volume = "7",
doi = "10.1016/j.ibror.2019.09.087",
pages = "S43"
}

Tatalović, N., Vidonja Uzelac, T., Oreščanin Dušić, Z., Nikolić-Kokić, A., Spasić, M.,& Blagojević, D.. (2019). Effects of ibogaine treatment on redox homeostasis and energy metabolism in rat. in IBRO Reports
Elsevier Ltd.., 7(Supplement), S43.
https://doi.org/10.1016/j.ibror.2019.09.087

Tatalović N, Vidonja Uzelac T, Oreščanin Dušić Z, Nikolić-Kokić A, Spasić M, Blagojević D. Effects of ibogaine treatment on redox homeostasis and energy metabolism in rat. in IBRO Reports. 2019;7(Supplement):S43.
doi:10.1016/j.ibror.2019.09.087 .

Tatalović, Nikola, Vidonja Uzelac, Teodora, Oreščanin Dušić, Zorana, Nikolić-Kokić, Aleksandra, Spasić, Mihajlo, Blagojević, Duško, "Effects of ibogaine treatment on redox homeostasis and energy metabolism in rat" in IBRO Reports, 7, no. Supplement (2019):S43,
https://doi.org/10.1016/j.ibror.2019.09.087 . .

TY  - JOUR
AU  - Vidonja Uzelac, Teodora
AU  - Tatalović, Nikola
AU  - Mijović, Milica
AU  - Koželj, Gordana
AU  - Nikolić-Kokić, Aleksandra
AU  - Oreščanin Dušić, Zorana
AU  - Bresjanac, Mara
AU  - Blagojević, Duško
PY  - 2019
UR  - http://www.doiserbia.nb.rs/Article.aspx?ID=0354-46641800055V
UR  - http://www.serbiosoc.org.rs/arch/index.php/abs/article/view/3420
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3353
AB  - Ibogaine, administered as a single oral dose (1-25 mg/kg body weight), has been used as an addiction-interrupting agent. Its effects persist for up to 72 h. Ex vivo results showed that ibogaine induced cellular energy consumption and restitution, followed by increased reactive oxygen species production and antioxidant activity. Therefore, the aim of this work was to explore the effect of a single oral dose of ibogaine (1 or 20 mg/kg body weight) on antioxidative defenses in rat liver and erythrocytes. Six and 24 h after ibogaine administration, histological examination showed glycogenolytic activity in hepatocytes, which was highest after 24 h in animals that received 20 mg/kg ibogaine. There were no changes in the activities of superoxide dismutases, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase in the liver and erythrocytes after ibogaine treatment, regardless of the dose. Hepatic xanthine oxidase activity was elevated in rats that received 20 mg/kg compared to the controls (p<0.01), suggesting faster adenosine turnover. TBARS concentration was elevated in the group treated with 1 mg/kg after 24 h compared to the controls (p<0.01), suggesting mild oxidative stress. Our results show that ibogaine treatment influenced hepatic redox homeostasis, but not sufficiently to remodel antioxidant enzyme activities at 6 and 24 h post-ibogaine application.
T2  - Archives of Biological Sciences
T1  - Effects of ibogaine per os application on redox homeostasis in rat liver and erythrocytes
IS  - 1
VL  - 71
DO  - 10.2298/ABS180918055V
SP  - 133
EP  - 144
ER  - 

@article{
author = "Vidonja Uzelac, Teodora and Tatalović, Nikola and Mijović, Milica and Koželj, Gordana and Nikolić-Kokić, Aleksandra and Oreščanin Dušić, Zorana and Bresjanac, Mara and Blagojević, Duško",
year = "2019",
abstract = "Ibogaine, administered as a single oral dose (1-25 mg/kg body weight), has been used as an addiction-interrupting agent. Its effects persist for up to 72 h. Ex vivo results showed that ibogaine induced cellular energy consumption and restitution, followed by increased reactive oxygen species production and antioxidant activity. Therefore, the aim of this work was to explore the effect of a single oral dose of ibogaine (1 or 20 mg/kg body weight) on antioxidative defenses in rat liver and erythrocytes. Six and 24 h after ibogaine administration, histological examination showed glycogenolytic activity in hepatocytes, which was highest after 24 h in animals that received 20 mg/kg ibogaine. There were no changes in the activities of superoxide dismutases, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase in the liver and erythrocytes after ibogaine treatment, regardless of the dose. Hepatic xanthine oxidase activity was elevated in rats that received 20 mg/kg compared to the controls (p<0.01), suggesting faster adenosine turnover. TBARS concentration was elevated in the group treated with 1 mg/kg after 24 h compared to the controls (p<0.01), suggesting mild oxidative stress. Our results show that ibogaine treatment influenced hepatic redox homeostasis, but not sufficiently to remodel antioxidant enzyme activities at 6 and 24 h post-ibogaine application.",
journal = "Archives of Biological Sciences",
title = "Effects of ibogaine per os application on redox homeostasis in rat liver and erythrocytes",
number = "1",
volume = "71",
doi = "10.2298/ABS180918055V",
pages = "133-144"
}

Vidonja Uzelac, T., Tatalović, N., Mijović, M., Koželj, G., Nikolić-Kokić, A., Oreščanin Dušić, Z., Bresjanac, M.,& Blagojević, D.. (2019). Effects of ibogaine per os application on redox homeostasis in rat liver and erythrocytes. in Archives of Biological Sciences, 71(1), 133-144.
https://doi.org/10.2298/ABS180918055V

Vidonja Uzelac T, Tatalović N, Mijović M, Koželj G, Nikolić-Kokić A, Oreščanin Dušić Z, Bresjanac M, Blagojević D. Effects of ibogaine per os application on redox homeostasis in rat liver and erythrocytes. in Archives of Biological Sciences. 2019;71(1):133-144.
doi:10.2298/ABS180918055V .

Vidonja Uzelac, Teodora, Tatalović, Nikola, Mijović, Milica, Koželj, Gordana, Nikolić-Kokić, Aleksandra, Oreščanin Dušić, Zorana, Bresjanac, Mara, Blagojević, Duško, "Effects of ibogaine per os application on redox homeostasis in rat liver and erythrocytes" in Archives of Biological Sciences, 71, no. 1 (2019):133-144,
https://doi.org/10.2298/ABS180918055V . .