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  - 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  - 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  - 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  - 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  - 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  - 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  - 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  - THES
AU  - Vidonja Uzelac, Teodora
PY  - 2019
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3473
AB  - Ibogain, primenjen u jediničnoj oralnoj dozi (1-25 mg/kg telesne mase (t.m)) se koristi kao agens u sprečavanju različitih oblika zavisnosti kod ljudi. Njegovi efekti traju i do 72 h. Ex vivo rezultati pokazuju da ibogain izaziva potrošnju energije u ćelijama i njenu restituciju, što je praćeno povećanjem stvaranja reaktivnih vrsta kiseonika i aktivnosti antioksidativne odbrane. Stoga je cilj ovog rada bio da istraži efekte jedinične oralne doze ibogaina (1 ili 20 mg/kg t.m.) na antioksidativnu odbranu u različitim tkivima pacova. Posle 6 i 24 h nakon ingestije ibogaina, histološka ispitivanja su pokazala pojačanu glikogenolitičku aktivnost hepatocita, koja je bila najviša posle 24 h kod životinja koje su primile 20 mg/kg ibogaina. Nije bilo promena u aktivnosti antioksidativnih enzimani u jetri ni u eritrocitima u tim periodima što ukazuje na izostanak sistemskog efekta na nivou oksidativnog pritiska. U jetri se povećala aktivnost ksantin oksidaze kod pacova koji su primili ibogain u dozi od 20 mg/kg u poređenju sa kontrolama što ukazuje na brži obrt adenozina. Nivo TBARS u jetri je povišen kod grupe tretirane sa 1 mg/kg posle 24 h u poređenju sa kontrolama što sugeriše postojanje umerenog oksidativnog stresa. U srcu je utvrđeno da ibogain nakon 6 h smanjuje količinu proteinskih -SH grupa što ukazuje na unutar-proteinsku oksidaciju, koja zajedno sa narušenom energetskom homeostazom može dovesti do promena u srčanom radu i nastanka diskretnih oštećenja. Ibogain inhibira ex vivo kontraktilnost ileuma u nivou doza ispod mM, pri čemu je efekat kod električne stimulacije, u odnosu na toničnu, značajno veći. Rezultati pretretmana na ileumu ex vivo ukazuju da ibogain svoje dejstvo ostvaruje delimično preko KATP kanala. Ibogain izaziva u ileumu ex vivo povećanje aktivnosti superoksid dismutaze (SOD) i katalaze (KAT), ali se ti efekti gube dodavanjem glibenklamida. Ibogain menja i redoks 7 ravnotežu u testisima, a nađeno povećanje aktivnosti SOD ukazuje na delikatnost očuvanja balansa koncentracija superoksida i vodonik peroksida koja se smatra krucijalnom u procesu kapacitacije spermatozoida. Rezultati pokazuju da ibogain u primenjenim dozama utiče na redoks status posmatranih tkiva i menja aktivnost antioksidativne odbrane, ali je odgovor visoko tkivno, dozno i vremenski specifičan, bez jasne zajedničke karakteristike.
AB  - Ibogaine, administered as a single oral dose (1-25 mg/kg body weight, (b.w.)), 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 b.w.) on antioxidative defenses in different rat tissues. 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 antioxidant enzymes in the liver and erythrocytes after ibogaine treatment, regardless of the dose. These results suggest there were no systemic ibogaine effects regarding antioxidant defense. Hepatic xanthine oxidase activity was elevated in rats that received 20 mg/kg compared to the controls, suggesting faster adenosine turnover. TBARS concentration was elevated in the group treated with 1 mg/kg after 24 h compared to the controls, suggesting mild oxidative stress. It was shown that ibogaine in heart after 6 h diminished the amount of protein -SH groups suggesting intra-protein oxidation, which along disturbed energetic homeostasis could lead to discrete cellular oxidative damages and possible heart failure. Ibogaine inhibited ex vivo ileum contractile activity with doses below mM. The effect was stronger in electrically stimulated contractions than tonic. Pretreatment with different potassium channel related agents showed that ibogaine obtained its inhibitory activity partially through KATP channels. Ibogaine induced the elevation of superoxide dismutase (SOD), catalase activity 9 ex vivo, but this effect was diminished by addition of glibenclamide. Ibogaine changed redox homeostasis in testicles as well, and elevated SOD activity suggested the importance of the preservation of delicate balance of superoxide and hydrogen peroxide concentrations that is crucial in sperm capacitation. Our results showed that ibogaine in doses applied in vivo per os influenced redox state and changed antioxidant activity, but response is highly tissue-, dose- and time- specific, without clear common characteristic.
PB  - Belgrade: Faculty of Medicine, University of Belgrade
T2  - Faculty of Medicine, University of Belgrade
T1  - Efekat ibogaina na sistem antioksidativne zaštite u perifernim tkivima i kontraktilnost terminalnog ileuma kod mužjaka pacova
T1  - Effect of ibogaine on antioxidative defense system in peripheral tissues and terminal ileum contractility in male rats
SP  - 1
EP  - 108
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3473
ER  - 

@phdthesis{
author = "Vidonja Uzelac, Teodora",
year = "2019",
abstract = "Ibogain, primenjen u jediničnoj oralnoj dozi (1-25 mg/kg telesne mase (t.m)) se koristi kao agens u sprečavanju različitih oblika zavisnosti kod ljudi. Njegovi efekti traju i do 72 h. Ex vivo rezultati pokazuju da ibogain izaziva potrošnju energije u ćelijama i njenu restituciju, što je praćeno povećanjem stvaranja reaktivnih vrsta kiseonika i aktivnosti antioksidativne odbrane. Stoga je cilj ovog rada bio da istraži efekte jedinične oralne doze ibogaina (1 ili 20 mg/kg t.m.) na antioksidativnu odbranu u različitim tkivima pacova. Posle 6 i 24 h nakon ingestije ibogaina, histološka ispitivanja su pokazala pojačanu glikogenolitičku aktivnost hepatocita, koja je bila najviša posle 24 h kod životinja koje su primile 20 mg/kg ibogaina. Nije bilo promena u aktivnosti antioksidativnih enzimani u jetri ni u eritrocitima u tim periodima što ukazuje na izostanak sistemskog efekta na nivou oksidativnog pritiska. U jetri se povećala aktivnost ksantin oksidaze kod pacova koji su primili ibogain u dozi od 20 mg/kg u poređenju sa kontrolama što ukazuje na brži obrt adenozina. Nivo TBARS u jetri je povišen kod grupe tretirane sa 1 mg/kg posle 24 h u poređenju sa kontrolama što sugeriše postojanje umerenog oksidativnog stresa. U srcu je utvrđeno da ibogain nakon 6 h smanjuje količinu proteinskih -SH grupa što ukazuje na unutar-proteinsku oksidaciju, koja zajedno sa narušenom energetskom homeostazom može dovesti do promena u srčanom radu i nastanka diskretnih oštećenja. Ibogain inhibira ex vivo kontraktilnost ileuma u nivou doza ispod mM, pri čemu je efekat kod električne stimulacije, u odnosu na toničnu, značajno veći. Rezultati pretretmana na ileumu ex vivo ukazuju da ibogain svoje dejstvo ostvaruje delimično preko KATP kanala. Ibogain izaziva u ileumu ex vivo povećanje aktivnosti superoksid dismutaze (SOD) i katalaze (KAT), ali se ti efekti gube dodavanjem glibenklamida. Ibogain menja i redoks 7 ravnotežu u testisima, a nađeno povećanje aktivnosti SOD ukazuje na delikatnost očuvanja balansa koncentracija superoksida i vodonik peroksida koja se smatra krucijalnom u procesu kapacitacije spermatozoida. Rezultati pokazuju da ibogain u primenjenim dozama utiče na redoks status posmatranih tkiva i menja aktivnost antioksidativne odbrane, ali je odgovor visoko tkivno, dozno i vremenski specifičan, bez jasne zajedničke karakteristike., Ibogaine, administered as a single oral dose (1-25 mg/kg body weight, (b.w.)), 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 b.w.) on antioxidative defenses in different rat tissues. 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 antioxidant enzymes in the liver and erythrocytes after ibogaine treatment, regardless of the dose. These results suggest there were no systemic ibogaine effects regarding antioxidant defense. Hepatic xanthine oxidase activity was elevated in rats that received 20 mg/kg compared to the controls, suggesting faster adenosine turnover. TBARS concentration was elevated in the group treated with 1 mg/kg after 24 h compared to the controls, suggesting mild oxidative stress. It was shown that ibogaine in heart after 6 h diminished the amount of protein -SH groups suggesting intra-protein oxidation, which along disturbed energetic homeostasis could lead to discrete cellular oxidative damages and possible heart failure. Ibogaine inhibited ex vivo ileum contractile activity with doses below mM. The effect was stronger in electrically stimulated contractions than tonic. Pretreatment with different potassium channel related agents showed that ibogaine obtained its inhibitory activity partially through KATP channels. Ibogaine induced the elevation of superoxide dismutase (SOD), catalase activity 9 ex vivo, but this effect was diminished by addition of glibenclamide. Ibogaine changed redox homeostasis in testicles as well, and elevated SOD activity suggested the importance of the preservation of delicate balance of superoxide and hydrogen peroxide concentrations that is crucial in sperm capacitation. Our results showed that ibogaine in doses applied in vivo per os influenced redox state and changed antioxidant activity, but response is highly tissue-, dose- and time- specific, without clear common characteristic.",
publisher = "Belgrade: Faculty of Medicine, University of Belgrade",
journal = "Faculty of Medicine, University of Belgrade",
title = "Efekat ibogaina na sistem antioksidativne zaštite u perifernim tkivima i kontraktilnost terminalnog ileuma kod mužjaka pacova, Effect of ibogaine on antioxidative defense system in peripheral tissues and terminal ileum contractility in male rats",
pages = "1-108",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3473"
}

Vidonja Uzelac, T.. (2019). Efekat ibogaina na sistem antioksidativne zaštite u perifernim tkivima i kontraktilnost terminalnog ileuma kod mužjaka pacova. in Faculty of Medicine, University of Belgrade
Belgrade: Faculty of Medicine, University of Belgrade., 1-108.
https://hdl.handle.net/21.15107/rcub_ibiss_3473

Vidonja Uzelac T. Efekat ibogaina na sistem antioksidativne zaštite u perifernim tkivima i kontraktilnost terminalnog ileuma kod mužjaka pacova. in Faculty of Medicine, University of Belgrade. 2019;:1-108.
https://hdl.handle.net/21.15107/rcub_ibiss_3473 .

Vidonja Uzelac, Teodora, "Efekat ibogaina na sistem antioksidativne zaštite u perifernim tkivima i kontraktilnost terminalnog ileuma kod mužjaka pacova" in Faculty of Medicine, University of Belgrade (2019):1-108,
https://hdl.handle.net/21.15107/rcub_ibiss_3473 .

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 . .

TY  - JOUR
AU  - Oreščanin Dušić, Zorana
AU  - Tatalović, Nikola
AU  - Vidonja Uzelac, Teodora
AU  - Brkljačić, Jelena
AU  - Nikolić-Kokić, Aleksandra
AU  - Mijušković, Ana
AU  - Spasić, Mihajlo
AU  - Paškulin, Roman
AU  - Bresjanac, Mara
AU  - Blagojević, Duško
PY  - 2018
UR  - https://www.hindawi.com/journals/omcl/2018/5969486/
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2970
AB  - Ibogaine is an indole alkaloid originally extracted from the root bark of the African rainforest shrub Tabernanthe iboga. It has been explored as a treatment for substance abuse because it interrupts drug addiction and relieves withdrawal symptoms. However, it has been shown that ibogaine treatment leads to a sharp and transient fall in cellular ATP level followed by an increase of cellular respiration and ROS production. Since contractile tissues are sensitive to changes in the levels of ATP and ROS, here we investigated an ibogaine-mediated link between altered redox homeostasis and uterine contractile activity. We found that low concentrations of ibogaine stimulated contractile activity in spontaneously active uteri, but incremental increase of doses inhibited it. Inhibitory concentrations of ibogaine led to decreased SOD1 and elevated GSH-Px activity, but doses that completely inhibited contractions increased CAT activity. Western blot analyses showed that changes in enzyme activities were not due to elevated enzyme protein concentrations but posttranslational modifications. Changes in antioxidant enzyme activities point to a vast concentration-dependent increase in H2O2 level. Knowing that extracellular ATP stimulates isolated uterus contractility, while H2O2 has an inhibitory effect, this concentration-dependent stimulation/inhibition could be linked to ibogaine-related alterations in ATP level and redox homeostasis.
T2  - Oxidative Medicine and Cellular Longevity
T1  - The Effects of Ibogaine on Uterine Smooth Muscle Contractions: Relation to the Activity of Antioxidant Enzymes
VL  - 2018
DO  - 10.1155/2018/5969486
SP  - 5969486
ER  - 

@article{
author = "Oreščanin Dušić, Zorana and Tatalović, Nikola and Vidonja Uzelac, Teodora and Brkljačić, Jelena and Nikolić-Kokić, Aleksandra and Mijušković, Ana and Spasić, Mihajlo and Paškulin, Roman and Bresjanac, Mara and Blagojević, Duško",
year = "2018",
abstract = "Ibogaine is an indole alkaloid originally extracted from the root bark of the African rainforest shrub Tabernanthe iboga. It has been explored as a treatment for substance abuse because it interrupts drug addiction and relieves withdrawal symptoms. However, it has been shown that ibogaine treatment leads to a sharp and transient fall in cellular ATP level followed by an increase of cellular respiration and ROS production. Since contractile tissues are sensitive to changes in the levels of ATP and ROS, here we investigated an ibogaine-mediated link between altered redox homeostasis and uterine contractile activity. We found that low concentrations of ibogaine stimulated contractile activity in spontaneously active uteri, but incremental increase of doses inhibited it. Inhibitory concentrations of ibogaine led to decreased SOD1 and elevated GSH-Px activity, but doses that completely inhibited contractions increased CAT activity. Western blot analyses showed that changes in enzyme activities were not due to elevated enzyme protein concentrations but posttranslational modifications. Changes in antioxidant enzyme activities point to a vast concentration-dependent increase in H2O2 level. Knowing that extracellular ATP stimulates isolated uterus contractility, while H2O2 has an inhibitory effect, this concentration-dependent stimulation/inhibition could be linked to ibogaine-related alterations in ATP level and redox homeostasis.",
journal = "Oxidative Medicine and Cellular Longevity",
title = "The Effects of Ibogaine on Uterine Smooth Muscle Contractions: Relation to the Activity of Antioxidant Enzymes",
volume = "2018",
doi = "10.1155/2018/5969486",
pages = "5969486"
}

Oreščanin Dušić, Z., Tatalović, N., Vidonja Uzelac, T., Brkljačić, J., Nikolić-Kokić, A., Mijušković, A., Spasić, M., Paškulin, R., Bresjanac, M.,& Blagojević, D.. (2018). The Effects of Ibogaine on Uterine Smooth Muscle Contractions: Relation to the Activity of Antioxidant Enzymes. in Oxidative Medicine and Cellular Longevity, 2018, 5969486.
https://doi.org/10.1155/2018/5969486

Oreščanin Dušić Z, Tatalović N, Vidonja Uzelac T, Brkljačić J, Nikolić-Kokić A, Mijušković A, Spasić M, Paškulin R, Bresjanac M, Blagojević D. The Effects of Ibogaine on Uterine Smooth Muscle Contractions: Relation to the Activity of Antioxidant Enzymes. in Oxidative Medicine and Cellular Longevity. 2018;2018:5969486.
doi:10.1155/2018/5969486 .

Oreščanin Dušić, Zorana, Tatalović, Nikola, Vidonja Uzelac, Teodora, Brkljačić, Jelena, Nikolić-Kokić, Aleksandra, Mijušković, Ana, Spasić, Mihajlo, Paškulin, Roman, Bresjanac, Mara, Blagojević, Duško, "The Effects of Ibogaine on Uterine Smooth Muscle Contractions: Relation to the Activity of Antioxidant Enzymes" in Oxidative Medicine and Cellular Longevity, 2018 (2018):5969486,
https://doi.org/10.1155/2018/5969486 . .

TY  - JOUR
AU  - Božić, Bojana
AU  - Vidonja Uzelac, Teodora
AU  - Kezić, Aleksandra
AU  - Bajčetić, Milica
PY  - 2018
UR  - http://www.eurekaselect.com/153927/article
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3052
AB  - Historically, quinidine was the first medicine used in the therapy of heart arrhythmias. Studies in the early 20th century identified quinidine, a diastereomer of the antimalarial quinine, as the most potent of the antiarrhythmic substances extracted from the cinchona plant. Quinidine is used by the 1920s, as an antiarrhythmic agent to maintain sinus rhythm after the conversion from atrial flutter or atrial fibrillation and to prevent recurrence of ventricular tachycardia or ventricular fibrillation. Its value in chronic prophylaxis of relapse of ventricular arrhythmia was brought under suspicion after publishing of meta analysis that showed that the application of quinidine increases mortality. Due to numerous proofs of increased risk for the appearance of ventricular arrhythmia and sudden death, as well as a number of other adverse effects and drug interactions, quinidine was withdrawn from use and in the recent years has become unavailable in many countries. On the other hand, recent studies have demonstrated that quinidine is the only oral medication that has consistently shown efficacy in preventing arrhythmias and terminating storms due to recurrent ventricular fibrillation, in patients with Brugada syndrome, idiopathic ventricular fibrillation and early repolarization syndrome. Quinidine is also the only antiarrhythmic drug that normalized the QT interval in patients with the congenital short QT syndrome. The aim of this review is to provide good insight into pro and contra arguments for quinidine use in ventricular arrhythmias evidence based on recently published literature.
T2  - Mini Reviews in Medicinal Chemistry
T1  - The Role of Quinidine in the Pharmacological Therapy of Ventricular Arrhythmias 'Quinidine'.
IS  - 6
VL  - 18
DO  - 10.2174/1389557517666170707110450
SP  - 468
EP  - 475
ER  - 

@article{
author = "Božić, Bojana and Vidonja Uzelac, Teodora and Kezić, Aleksandra and Bajčetić, Milica",
year = "2018",
abstract = "Historically, quinidine was the first medicine used in the therapy of heart arrhythmias. Studies in the early 20th century identified quinidine, a diastereomer of the antimalarial quinine, as the most potent of the antiarrhythmic substances extracted from the cinchona plant. Quinidine is used by the 1920s, as an antiarrhythmic agent to maintain sinus rhythm after the conversion from atrial flutter or atrial fibrillation and to prevent recurrence of ventricular tachycardia or ventricular fibrillation. Its value in chronic prophylaxis of relapse of ventricular arrhythmia was brought under suspicion after publishing of meta analysis that showed that the application of quinidine increases mortality. Due to numerous proofs of increased risk for the appearance of ventricular arrhythmia and sudden death, as well as a number of other adverse effects and drug interactions, quinidine was withdrawn from use and in the recent years has become unavailable in many countries. On the other hand, recent studies have demonstrated that quinidine is the only oral medication that has consistently shown efficacy in preventing arrhythmias and terminating storms due to recurrent ventricular fibrillation, in patients with Brugada syndrome, idiopathic ventricular fibrillation and early repolarization syndrome. Quinidine is also the only antiarrhythmic drug that normalized the QT interval in patients with the congenital short QT syndrome. The aim of this review is to provide good insight into pro and contra arguments for quinidine use in ventricular arrhythmias evidence based on recently published literature.",
journal = "Mini Reviews in Medicinal Chemistry",
title = "The Role of Quinidine in the Pharmacological Therapy of Ventricular Arrhythmias 'Quinidine'.",
number = "6",
volume = "18",
doi = "10.2174/1389557517666170707110450",
pages = "468-475"
}

Božić, B., Vidonja Uzelac, T., Kezić, A.,& Bajčetić, M.. (2018). The Role of Quinidine in the Pharmacological Therapy of Ventricular Arrhythmias 'Quinidine'.. in Mini Reviews in Medicinal Chemistry, 18(6), 468-475.
https://doi.org/10.2174/1389557517666170707110450

Božić B, Vidonja Uzelac T, Kezić A, Bajčetić M. The Role of Quinidine in the Pharmacological Therapy of Ventricular Arrhythmias 'Quinidine'.. in Mini Reviews in Medicinal Chemistry. 2018;18(6):468-475.
doi:10.2174/1389557517666170707110450 .

Božić, Bojana, Vidonja Uzelac, Teodora, Kezić, Aleksandra, Bajčetić, Milica, "The Role of Quinidine in the Pharmacological Therapy of Ventricular Arrhythmias 'Quinidine'." in Mini Reviews in Medicinal Chemistry, 18, no. 6 (2018):468-475,
https://doi.org/10.2174/1389557517666170707110450 . .

TY  - CONF
AU  - Tatalović, Nikola
AU  - Vidonja Uzelac, Teodora
AU  - Oreščanin Dušić, Zorana
AU  - Brkljačić, Jelena
AU  - Nikolić-Kokić, Aleksandra
AU  - Mijušković, Ana
AU  - Spasić, Mihajlo
AU  - Paškulin, Roman
AU  - Bresjanac, Maja
AU  - Blagojević, Duško
PY  - 2017
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4044
AB  - The ibogaine drug is originated from the rainforest shrub Tabernanthe iboga, which grows in West Africa. The tribes of the Gabon have used the iboga plant root bark as a stimulant, for medicinal purposes, and in rite of passage ceremonies, for centuries. In the western world ibogaine is mostly known for its ability to inspire a sense of wellbeing both mentally and physically. Ibogaine has also been used for the treatment of substance abuse because it interrupts drug addiction, relieves withdrawal symptoms, and significantly decreases the desire for cocaine, heroin, alcohol and most other mind altering drugs. Now it is known that the pharmacology of ibogaine is quite complex and affects many different neurotransmitter systems simultaneously. Ibogaine binds to several types of receptors: 5-Hydroxytryptamine (5-HT), opioid, nicotinic and N-methyl-D-aspartate (NMDA) receptors, dopaminergic and 5-HT transporters and monoamine oxidase enzyme (MAO) 1. Although the mechanisms of ibogaine action in neural tissue are well studied, the effects on peripheral tissues are poorly understood. 
Paskulin et al. have shown that ibogaine causes a sharp and transient fall in cellular ATP level in yeast, which was followed by an immediate increase in respiration and CO2 production, in a time and concentration dependent manner 2, 3. Increased respiration leads to increase of ROS production and subsequent activation of antioxidant enzymes. These effects of ibogaine are not mediated by receptor binding and are not tissue and species specific 2, 4. It was previously shown that ibogaine-induced fall in cellular ATP level was caused by increased ATP consumption. The process in which the consumption of ATP is increased remains unclear. The proteome changes (induction of energy metabolism enzymes, antioxidant enzymes and numerous low abundance proteins) are responsible for at least a part of initial energy expenditures in ibogaine-treated yeast 5, 2. Study on human blood erythrocytes 4 showed that ibogaine leads to release of ATP in the blood plasma. Ibogaine doesn’t have any significant in vitro antioxidant properties per se but it influences physiological oxidative stress defence system in pro-antioxidant manner 3, 4.
In this study, we examined the effects of ibogaine on the model of the isolated rat uterus. Contractile tissues are sensitive to ATP levels and the depletion of energetics could lead to the impairment of regular rhythms and reversible relaxation. Extracellular ATP is known to stimulate uterine contractions in different species but the exact underlying mechanisms are poorly investigated. Furthermore, different contractile tissues, including uterus, are also sensitive to ROS, especially hydrogen peroxide (H2O2) 6. Antioxidant enzyme cytosolic copper-zinc containing superoxide dismutase (SOD1) can also affect the contractility of uterine smooth muscles 7. All these make the isolated contractile tissues a good model for examining the effects of ibogaine on both redox homeostasis and pharmacodinamics.
Unlike isolated arteries and ileum8, the uterus may have a wide range of different types and intensities of contractile activity depending on the properties of the isotonic solution. This allows us to register not only the relaxant but also the stimulatory effect of the tested substance. The aim of this study was to investigate the effects of ibogaine on both contractile properties of uterus and redox homeostasis and explore the possible link between between the two.
Overall, ibogaine treatment has altered redox homeostasis and affected contractile properties of uterus. Ibogaine had the opposite effects on spontaneously active rat uteri depending on the applied concentration. Lower concentrations increased force of contraction, amplitude, frequency and duration of individual contractions. Higher concentrations caused concentration dependent relaxation of spontaneously active uteri. On the other hand, when the uterus is contracting with a high intensity (when exposed to higher Ca2+ concentrations) ibogaine showed only a relaxant effect.
The increase in uterine contractile activity after treatment with low doses of ibogaine could be partly attributed to possible increase in the extracellular concentration of ATP. However, the ATP leads only to a moderate increase in the intensity of uterine contractility, without affecting the character of contractions (i.e. their regularity), whereas ibogaine has a pronounced pace making effect.
Ibogaine also had a concentration dependant effect on the activity of antioxidant enzymes suggesting a vast, increase in cellular respiration and H2O2 level. Ibogaine mediated relaxation found in the present study can be attributed to the influence of H2O2. However, the other possible mechanisms of ibogaine induced smooth muscle relaxation cannot be eliminated, regarding to its wide range of interaction with different receptors and signal transduction pathways.
The results regarding energy metabolism and redox homeostasis are in accordance with the previous observations in different experimental models. Research on an isolated uterus has allowed us to further examine the mechanism of this phenomenon: whether the increase in the intensity of cellular respiration is the result of an increased contractile activity that is caused by ibogaine? Only partially, because ibogaine leads to an increase that is several times greater compared to the uterus with phasic contractile activity of maximal intensity, induced by extracellular Ca2+, indicating the existence of ibogaines tissue non-specific ways of energy metabolism induction.
PB  - Belgrade : Faculty of Chemistry
PB  - Belgrade : Serbian Biochemical Society
C3  - Serbian Biochemical Society  Seventh Conference with international participation; Biochemistry of Control in Life and Technology; Proceedings
T1  - The effects of ibogaine on uterine redox homeostasis and contractility
SP  - 203
EP  - 205
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4044
ER  - 

@conference{
author = "Tatalović, Nikola and Vidonja Uzelac, Teodora and Oreščanin Dušić, Zorana and Brkljačić, Jelena and Nikolić-Kokić, Aleksandra and Mijušković, Ana and Spasić, Mihajlo and Paškulin, Roman and Bresjanac, Maja and Blagojević, Duško",
year = "2017",
abstract = "The ibogaine drug is originated from the rainforest shrub Tabernanthe iboga, which grows in West Africa. The tribes of the Gabon have used the iboga plant root bark as a stimulant, for medicinal purposes, and in rite of passage ceremonies, for centuries. In the western world ibogaine is mostly known for its ability to inspire a sense of wellbeing both mentally and physically. Ibogaine has also been used for the treatment of substance abuse because it interrupts drug addiction, relieves withdrawal symptoms, and significantly decreases the desire for cocaine, heroin, alcohol and most other mind altering drugs. Now it is known that the pharmacology of ibogaine is quite complex and affects many different neurotransmitter systems simultaneously. Ibogaine binds to several types of receptors: 5-Hydroxytryptamine (5-HT), opioid, nicotinic and N-methyl-D-aspartate (NMDA) receptors, dopaminergic and 5-HT transporters and monoamine oxidase enzyme (MAO) 1. Although the mechanisms of ibogaine action in neural tissue are well studied, the effects on peripheral tissues are poorly understood. 
Paskulin et al. have shown that ibogaine causes a sharp and transient fall in cellular ATP level in yeast, which was followed by an immediate increase in respiration and CO2 production, in a time and concentration dependent manner 2, 3. Increased respiration leads to increase of ROS production and subsequent activation of antioxidant enzymes. These effects of ibogaine are not mediated by receptor binding and are not tissue and species specific 2, 4. It was previously shown that ibogaine-induced fall in cellular ATP level was caused by increased ATP consumption. The process in which the consumption of ATP is increased remains unclear. The proteome changes (induction of energy metabolism enzymes, antioxidant enzymes and numerous low abundance proteins) are responsible for at least a part of initial energy expenditures in ibogaine-treated yeast 5, 2. Study on human blood erythrocytes 4 showed that ibogaine leads to release of ATP in the blood plasma. Ibogaine doesn’t have any significant in vitro antioxidant properties per se but it influences physiological oxidative stress defence system in pro-antioxidant manner 3, 4.
In this study, we examined the effects of ibogaine on the model of the isolated rat uterus. Contractile tissues are sensitive to ATP levels and the depletion of energetics could lead to the impairment of regular rhythms and reversible relaxation. Extracellular ATP is known to stimulate uterine contractions in different species but the exact underlying mechanisms are poorly investigated. Furthermore, different contractile tissues, including uterus, are also sensitive to ROS, especially hydrogen peroxide (H2O2) 6. Antioxidant enzyme cytosolic copper-zinc containing superoxide dismutase (SOD1) can also affect the contractility of uterine smooth muscles 7. All these make the isolated contractile tissues a good model for examining the effects of ibogaine on both redox homeostasis and pharmacodinamics.
Unlike isolated arteries and ileum8, the uterus may have a wide range of different types and intensities of contractile activity depending on the properties of the isotonic solution. This allows us to register not only the relaxant but also the stimulatory effect of the tested substance. The aim of this study was to investigate the effects of ibogaine on both contractile properties of uterus and redox homeostasis and explore the possible link between between the two.
Overall, ibogaine treatment has altered redox homeostasis and affected contractile properties of uterus. Ibogaine had the opposite effects on spontaneously active rat uteri depending on the applied concentration. Lower concentrations increased force of contraction, amplitude, frequency and duration of individual contractions. Higher concentrations caused concentration dependent relaxation of spontaneously active uteri. On the other hand, when the uterus is contracting with a high intensity (when exposed to higher Ca2+ concentrations) ibogaine showed only a relaxant effect.
The increase in uterine contractile activity after treatment with low doses of ibogaine could be partly attributed to possible increase in the extracellular concentration of ATP. However, the ATP leads only to a moderate increase in the intensity of uterine contractility, without affecting the character of contractions (i.e. their regularity), whereas ibogaine has a pronounced pace making effect.
Ibogaine also had a concentration dependant effect on the activity of antioxidant enzymes suggesting a vast, increase in cellular respiration and H2O2 level. Ibogaine mediated relaxation found in the present study can be attributed to the influence of H2O2. However, the other possible mechanisms of ibogaine induced smooth muscle relaxation cannot be eliminated, regarding to its wide range of interaction with different receptors and signal transduction pathways.
The results regarding energy metabolism and redox homeostasis are in accordance with the previous observations in different experimental models. Research on an isolated uterus has allowed us to further examine the mechanism of this phenomenon: whether the increase in the intensity of cellular respiration is the result of an increased contractile activity that is caused by ibogaine? Only partially, because ibogaine leads to an increase that is several times greater compared to the uterus with phasic contractile activity of maximal intensity, induced by extracellular Ca2+, indicating the existence of ibogaines tissue non-specific ways of energy metabolism induction.",
publisher = "Belgrade : Faculty of Chemistry, Belgrade : Serbian Biochemical Society",
journal = "Serbian Biochemical Society  Seventh Conference with international participation; Biochemistry of Control in Life and Technology; Proceedings",
title = "The effects of ibogaine on uterine redox homeostasis and contractility",
pages = "203-205",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4044"
}

Tatalović, N., Vidonja Uzelac, T., Oreščanin Dušić, Z., Brkljačić, J., Nikolić-Kokić, A., Mijušković, A., Spasić, M., Paškulin, R., Bresjanac, M.,& Blagojević, D.. (2017). The effects of ibogaine on uterine redox homeostasis and contractility. in Serbian Biochemical Society  Seventh Conference with international participation; Biochemistry of Control in Life and Technology; Proceedings
Belgrade : Faculty of Chemistry., 203-205.
https://hdl.handle.net/21.15107/rcub_ibiss_4044

Tatalović N, Vidonja Uzelac T, Oreščanin Dušić Z, Brkljačić J, Nikolić-Kokić A, Mijušković A, Spasić M, Paškulin R, Bresjanac M, Blagojević D. The effects of ibogaine on uterine redox homeostasis and contractility. in Serbian Biochemical Society  Seventh Conference with international participation; Biochemistry of Control in Life and Technology; Proceedings. 2017;:203-205.
https://hdl.handle.net/21.15107/rcub_ibiss_4044 .

Tatalović, Nikola, Vidonja Uzelac, Teodora, Oreščanin Dušić, Zorana, Brkljačić, Jelena, Nikolić-Kokić, Aleksandra, Mijušković, Ana, Spasić, Mihajlo, Paškulin, Roman, Bresjanac, Maja, Blagojević, Duško, "The effects of ibogaine on uterine redox homeostasis and contractility" in Serbian Biochemical Society  Seventh Conference with international participation; Biochemistry of Control in Life and Technology; Proceedings (2017):203-205,
https://hdl.handle.net/21.15107/rcub_ibiss_4044 .

TY  - CONF
AU  - Tatalović, Nikola
AU  - Vidonja Uzelac, Teodora
AU  - Mijušković, Ana
AU  - Oreščanin Dušić, Zorana
AU  - Nikolić-Kokić, Aleksandra
AU  - Spasić, Mihajlo
AU  - Bresjanac, Maja
AU  - Paškulin, Roman
AU  - Blagojević, Duško
PY  - 2017
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4279
AB  - The anti-addiction agent ibogaine interacts with different types of neural transmitter receptors, but also decrease cellular ATP level, followed by increased cellular respiration and production
of reactive oxygen species, which change redox homeostasis. We wanted to investigate the effects of single dose of 1 or 20 mg/kg body weight of ibogaine (dose range commonly used for therapeutic
purposes) on activity of antioxidant enzymes (SOD1 and SOD2, catalase - CAT, glutathione peroxidase - GSH-Px, glutathione reductase - GR and glutathione S transferase - GST) in
rat uterus, 6 and 24 h after treatment. Three month-old virgin female rats were treated per os while in estrus phase of estrous cycle (determined by examination of vaginal smear). A problem
in this experimental design was that activity of antioxidant enzymes changes during the estrous cycle (SOD2 activity is lower, GSH-Px and GR activities are higher in estrus compared to
metestrus). Since estrus phase lasts 15–24 h, the female rats treated in estrus, after 6 h will still be in estrus, in most cases, but after 24 h they will be in metestrus. Therefore we used two
approaches for 6 h treatment. First, females were treated immediately upon completion of vaginal smear, and sacrificed 6 h later (in the time of treatment they were in estrus phase). The others
were treated with a delay of 18 h, and sacrificed 6 h later, so that in the time of sacrifice, they were in the same phase as the 24 h group (metestrus). The dose of 20 mg/kg has lowered CAT activity,
but, in general, canonical discriminant analysis shows that the phase of the estrous cycle in the time of sacrifice has a greater impact than a dose of ibogaine. Thus, selection of the phase of
the cycle, appropriate control groups and statistical model are of crucial importance in order to distinguish the effects of treatment from the effects of estrous cycle phase changes.
PB  - Bologna: Federation of European Physiological Societies
C3  - 42nd FEBS Congress, From Molecules to Cells and Back; 2017 Sep 10-14; Jerusalem, Israel
T1  - Determining short-term effects on the activity of antioxidant enzymes in the rat uterus: the example of ibogaine
IS  - Suppl. 1
VL  - 284
DO  - 10.1111/febs.14174
SP  - 233
EP  - 233
ER  - 

@conference{
author = "Tatalović, Nikola and Vidonja Uzelac, Teodora and Mijušković, Ana and Oreščanin Dušić, Zorana and Nikolić-Kokić, Aleksandra and Spasić, Mihajlo and Bresjanac, Maja and Paškulin, Roman and Blagojević, Duško",
year = "2017",
abstract = "The anti-addiction agent ibogaine interacts with different types of neural transmitter receptors, but also decrease cellular ATP level, followed by increased cellular respiration and production
of reactive oxygen species, which change redox homeostasis. We wanted to investigate the effects of single dose of 1 or 20 mg/kg body weight of ibogaine (dose range commonly used for therapeutic
purposes) on activity of antioxidant enzymes (SOD1 and SOD2, catalase - CAT, glutathione peroxidase - GSH-Px, glutathione reductase - GR and glutathione S transferase - GST) in
rat uterus, 6 and 24 h after treatment. Three month-old virgin female rats were treated per os while in estrus phase of estrous cycle (determined by examination of vaginal smear). A problem
in this experimental design was that activity of antioxidant enzymes changes during the estrous cycle (SOD2 activity is lower, GSH-Px and GR activities are higher in estrus compared to
metestrus). Since estrus phase lasts 15–24 h, the female rats treated in estrus, after 6 h will still be in estrus, in most cases, but after 24 h they will be in metestrus. Therefore we used two
approaches for 6 h treatment. First, females were treated immediately upon completion of vaginal smear, and sacrificed 6 h later (in the time of treatment they were in estrus phase). The others
were treated with a delay of 18 h, and sacrificed 6 h later, so that in the time of sacrifice, they were in the same phase as the 24 h group (metestrus). The dose of 20 mg/kg has lowered CAT activity,
but, in general, canonical discriminant analysis shows that the phase of the estrous cycle in the time of sacrifice has a greater impact than a dose of ibogaine. Thus, selection of the phase of
the cycle, appropriate control groups and statistical model are of crucial importance in order to distinguish the effects of treatment from the effects of estrous cycle phase changes.",
publisher = "Bologna: Federation of European Physiological Societies",
journal = "42nd FEBS Congress, From Molecules to Cells and Back; 2017 Sep 10-14; Jerusalem, Israel",
title = "Determining short-term effects on the activity of antioxidant enzymes in the rat uterus: the example of ibogaine",
number = "Suppl. 1",
volume = "284",
doi = "10.1111/febs.14174",
pages = "233-233"
}

Tatalović, N., Vidonja Uzelac, T., Mijušković, A., Oreščanin Dušić, Z., Nikolić-Kokić, A., Spasić, M., Bresjanac, M., Paškulin, R.,& Blagojević, D.. (2017). Determining short-term effects on the activity of antioxidant enzymes in the rat uterus: the example of ibogaine. in 42nd FEBS Congress, From Molecules to Cells and Back; 2017 Sep 10-14; Jerusalem, Israel
Bologna: Federation of European Physiological Societies., 284(Suppl. 1), 233-233.
https://doi.org/10.1111/febs.14174

Tatalović N, Vidonja Uzelac T, Mijušković A, Oreščanin Dušić Z, Nikolić-Kokić A, Spasić M, Bresjanac M, Paškulin R, Blagojević D. Determining short-term effects on the activity of antioxidant enzymes in the rat uterus: the example of ibogaine. in 42nd FEBS Congress, From Molecules to Cells and Back; 2017 Sep 10-14; Jerusalem, Israel. 2017;284(Suppl. 1):233-233.
doi:10.1111/febs.14174 .

Tatalović, Nikola, Vidonja Uzelac, Teodora, Mijušković, Ana, Oreščanin Dušić, Zorana, Nikolić-Kokić, Aleksandra, Spasić, Mihajlo, Bresjanac, Maja, Paškulin, Roman, Blagojević, Duško, "Determining short-term effects on the activity of antioxidant enzymes in the rat uterus: the example of ibogaine" in 42nd FEBS Congress, From Molecules to Cells and Back; 2017 Sep 10-14; Jerusalem, Israel, 284, no. Suppl. 1 (2017):233-233,
https://doi.org/10.1111/febs.14174 . .

TY  - CONF
AU  - Vidonja Uzelac, Teodora
AU  - Tatalović, Nikola
AU  - Koželj, Gordana
AU  - Oreščanin Dušić, Zorana
AU  - Nikolić-Kokić, Aleksandra
AU  - Spasić, Mihajlo
AU  - Paškulin, Roman
AU  - Bresjanac, Maja
AU  - Blagojević, Duško
PY  - 2017
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4045
AB  - For centuries, plant T. iboga was used in African tribal communities for different ritual
purposes. Beseades its stimulant effects in the last few decades ibogaine has been used as
antiaddiction supstance against nicotine, alcohol, stimulants and opiates 1. Ibogain is not
registered as a cure, but it is posibile to purchase capsule with ibogaine through websites 2.
Ibogaine binds to different types of receptors and neurotransmitter transporters in brain 3. It
also influences cellular energy, redox state and antioxidant capacity in a dose- and timedependent
manner. In yeast, ibogaine decreases cellular ATP level and increases CO2
production in the first hour after exposure, followed by increased cellular respiration and
the production of reactive oxygen species (ROS) after 5 h 4-6. Ibogain is metabolized in the
liver by CYP2D6, and its pharmacologically active metabolite noribogaine is formed by
demethylation. Both are excreted via gastrointestinal and renal tracts within 24 h 3.
In this experiment 30 male Wistar rats, 3 months old, 200-250 g body weight (b.w.) were
treated per os once with either 1 or 20 mg/kg b.w. of ibogaine. After 6 h and 24 h from
treatments, the concentrations of ibogaine and noribogaine were measured in the blood
plasma, as well as the activity of antioxidant enzymes: catalase (CAT), glutathione
peroxidase (GPx), glutathione reductase (GR) and superoxide dismutase 1 (SOD1) in
erythrocytes and liver. In liver, the activity of SOD2 and glutathione S transferase (GST)
were also measured. The control group was treated with dH2O. All studies were approved
by the Local Animal Care Committee.
Measurement of ibogaine and noribogaine concentrations in the blood plasma showed
dominant presence of noribogaine against ibogaine 6 h after treatment, while after 24 h
only noribogaine was present in traces. The concentration of ibogaine and noribogaine was
higher in the group treated with 20 mg/kg b.w. The presence of noribogaine in higher
concentrations than ibogaine 6 h after treatment is consistent with pharmacokinetics of
ibogaine. Our results showed that ibogaine treatment with both doses did not change the
activity of antioxidant enzymes in erythrocytes and liver after neither 6 nor 24 h.
After entering the circulation, ibogaine quickly becomes available to tissues. After the first
pass in liver, it is metabolized to noribogaine that is also pharmacologically active 3.
However, despite liver activity in ibogaine metabolism and transformation that
additionally produce ROS and ibogaine redox potential, no changes of the activity of
antioxidant enzymes were measured in the liver. It is possible that ibogaine in applied
doses is not so effective or liver has large antioxidant potential and resolve ibogainemediated
redox disequilibrium much earlier than 6 or 24 h.
Ibogine in vitro affected the activity of SOD1 and GR in erythrocytes, but in higher
concentration and for 1 h period 6. Treatment with ibogaine in this experiment yielded
lower amount of ibogaine in the blood plasma that could influence erythrocytes antioxidant
enzymes and the activity measurements were performed after 6 and 24 h. That’s are some
of possible explanations for the lack of changes in the activity of antioxidant enzymes in
erythrocytes in this experiment.
Our previous results on ileum (where changes of the activity of antioxidant enzymes were
measured) suggests tissue specific ibogaine influence and a combination of its
pharmacological and redox mediated effects 7.
PB  - Belgrade : Faculty of Chemistry
PB  - Belgrade : Serbian Biochemical Society
C3  - Serbian Biochemical Society  Seventh Conference with international participation; Biochemistry of Control in Life and Technology; Proceedings
T1  - Ibogaine redox potential - the effects on antioxidant enzymes after ingestion
SP  - 211
EP  - 212
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4045
ER  - 

@conference{
author = "Vidonja Uzelac, Teodora and Tatalović, Nikola and Koželj, Gordana and Oreščanin Dušić, Zorana and Nikolić-Kokić, Aleksandra and Spasić, Mihajlo and Paškulin, Roman and Bresjanac, Maja and Blagojević, Duško",
year = "2017",
abstract = "For centuries, plant T. iboga was used in African tribal communities for different ritual
purposes. Beseades its stimulant effects in the last few decades ibogaine has been used as
antiaddiction supstance against nicotine, alcohol, stimulants and opiates 1. Ibogain is not
registered as a cure, but it is posibile to purchase capsule with ibogaine through websites 2.
Ibogaine binds to different types of receptors and neurotransmitter transporters in brain 3. It
also influences cellular energy, redox state and antioxidant capacity in a dose- and timedependent
manner. In yeast, ibogaine decreases cellular ATP level and increases CO2
production in the first hour after exposure, followed by increased cellular respiration and
the production of reactive oxygen species (ROS) after 5 h 4-6. Ibogain is metabolized in the
liver by CYP2D6, and its pharmacologically active metabolite noribogaine is formed by
demethylation. Both are excreted via gastrointestinal and renal tracts within 24 h 3.
In this experiment 30 male Wistar rats, 3 months old, 200-250 g body weight (b.w.) were
treated per os once with either 1 or 20 mg/kg b.w. of ibogaine. After 6 h and 24 h from
treatments, the concentrations of ibogaine and noribogaine were measured in the blood
plasma, as well as the activity of antioxidant enzymes: catalase (CAT), glutathione
peroxidase (GPx), glutathione reductase (GR) and superoxide dismutase 1 (SOD1) in
erythrocytes and liver. In liver, the activity of SOD2 and glutathione S transferase (GST)
were also measured. The control group was treated with dH2O. All studies were approved
by the Local Animal Care Committee.
Measurement of ibogaine and noribogaine concentrations in the blood plasma showed
dominant presence of noribogaine against ibogaine 6 h after treatment, while after 24 h
only noribogaine was present in traces. The concentration of ibogaine and noribogaine was
higher in the group treated with 20 mg/kg b.w. The presence of noribogaine in higher
concentrations than ibogaine 6 h after treatment is consistent with pharmacokinetics of
ibogaine. Our results showed that ibogaine treatment with both doses did not change the
activity of antioxidant enzymes in erythrocytes and liver after neither 6 nor 24 h.
After entering the circulation, ibogaine quickly becomes available to tissues. After the first
pass in liver, it is metabolized to noribogaine that is also pharmacologically active 3.
However, despite liver activity in ibogaine metabolism and transformation that
additionally produce ROS and ibogaine redox potential, no changes of the activity of
antioxidant enzymes were measured in the liver. It is possible that ibogaine in applied
doses is not so effective or liver has large antioxidant potential and resolve ibogainemediated
redox disequilibrium much earlier than 6 or 24 h.
Ibogine in vitro affected the activity of SOD1 and GR in erythrocytes, but in higher
concentration and for 1 h period 6. Treatment with ibogaine in this experiment yielded
lower amount of ibogaine in the blood plasma that could influence erythrocytes antioxidant
enzymes and the activity measurements were performed after 6 and 24 h. That’s are some
of possible explanations for the lack of changes in the activity of antioxidant enzymes in
erythrocytes in this experiment.
Our previous results on ileum (where changes of the activity of antioxidant enzymes were
measured) suggests tissue specific ibogaine influence and a combination of its
pharmacological and redox mediated effects 7.",
publisher = "Belgrade : Faculty of Chemistry, Belgrade : Serbian Biochemical Society",
journal = "Serbian Biochemical Society  Seventh Conference with international participation; Biochemistry of Control in Life and Technology; Proceedings",
title = "Ibogaine redox potential - the effects on antioxidant enzymes after ingestion",
pages = "211-212",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4045"
}

Vidonja Uzelac, T., Tatalović, N., Koželj, G., Oreščanin Dušić, Z., Nikolić-Kokić, A., Spasić, M., Paškulin, R., Bresjanac, M.,& Blagojević, D.. (2017). Ibogaine redox potential - the effects on antioxidant enzymes after ingestion. in Serbian Biochemical Society  Seventh Conference with international participation; Biochemistry of Control in Life and Technology; Proceedings
Belgrade : Faculty of Chemistry., 211-212.
https://hdl.handle.net/21.15107/rcub_ibiss_4045

Vidonja Uzelac T, Tatalović N, Koželj G, Oreščanin Dušić Z, Nikolić-Kokić A, Spasić M, Paškulin R, Bresjanac M, Blagojević D. Ibogaine redox potential - the effects on antioxidant enzymes after ingestion. in Serbian Biochemical Society  Seventh Conference with international participation; Biochemistry of Control in Life and Technology; Proceedings. 2017;:211-212.
https://hdl.handle.net/21.15107/rcub_ibiss_4045 .

Vidonja Uzelac, Teodora, Tatalović, Nikola, Koželj, Gordana, Oreščanin Dušić, Zorana, Nikolić-Kokić, Aleksandra, Spasić, Mihajlo, Paškulin, Roman, Bresjanac, Maja, Blagojević, Duško, "Ibogaine redox potential - the effects on antioxidant enzymes after ingestion" in Serbian Biochemical Society  Seventh Conference with international participation; Biochemistry of Control in Life and Technology; Proceedings (2017):211-212,
https://hdl.handle.net/21.15107/rcub_ibiss_4045 .

TY  - JOUR
AU  - Trailović, Saša M.
AU  - Marjanović, Đorđe S.
AU  - Vidonja Uzelac, Teodora
AU  - Milovanović, Mirjana
AU  - Nedeljković Trailović, Jelena
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0034528817300103
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2552
AB  - Acute poisoning with OPs may lead to a range of neurological effects, which cannot be explained by AChE inhibition alone. Several OPs interact directly with cholinergic receptors in mammals, but such data does not exist for invertebrates. The aim of current study was to investigate the direct and indirect effects of diazinon on the contractions of rat ileum and to compare those effects on the nervemuscle preparation of the Ascaris suum. In the presence of increasing concentrations of diazinon (3, 10 and 30 nM), EFS-induced ileal contractions were increased significantly. In the same preparation, diazinon 3 nM, significantly increased contractions induced by EFS, but did not affect the contractions caused by 5MFI. Contrarily, 1 μM of diazinon significantly and reversibly inhibited the EFS-induced ileal contractions. Diazinon exhibited competitive and non-competitive inhibitions of 5MFI induced contractions. The control EC50 of 5MFI was 2.48 μM with Rmax = 1.88 g. In the presence of diazinon, EC50 was 12.45 μM, while Rmax was reduced to 0.43 g. After washing, the EC50 and Rmax values were again closer to the control level (3.80 μM and 1.04 g). Diazinon 1 μM did not inhibit Ascaris suum contractions caused by ACh, but it increased the Rmax. Diazinon in our study exhibits two opposite effects on the motor activity of the ileum. In low nanomolar concentrations the dominat is its effect on AChE and the stimulation of contractions. Furthermore, in concentrations that approach micromolar values diazinon has a direct inhibitory effect on muscarinic receptors. The direct inhibitory effect of diazinon on A. suum contractions was not found.
T2  - Research in Veterinary Science
T1  - Two opposite dose-dependent effects of diazinon on the motor activity of the rat ileum
IS  - 2
VL  - 112
DO  - 10.1016/j.rvsc.2017.01.002
SP  - 18
EP  - 25
ER  - 

@article{
author = "Trailović, Saša M. and Marjanović, Đorđe S. and Vidonja Uzelac, Teodora and Milovanović, Mirjana and Nedeljković Trailović, Jelena",
year = "2017",
abstract = "Acute poisoning with OPs may lead to a range of neurological effects, which cannot be explained by AChE inhibition alone. Several OPs interact directly with cholinergic receptors in mammals, but such data does not exist for invertebrates. The aim of current study was to investigate the direct and indirect effects of diazinon on the contractions of rat ileum and to compare those effects on the nervemuscle preparation of the Ascaris suum. In the presence of increasing concentrations of diazinon (3, 10 and 30 nM), EFS-induced ileal contractions were increased significantly. In the same preparation, diazinon 3 nM, significantly increased contractions induced by EFS, but did not affect the contractions caused by 5MFI. Contrarily, 1 μM of diazinon significantly and reversibly inhibited the EFS-induced ileal contractions. Diazinon exhibited competitive and non-competitive inhibitions of 5MFI induced contractions. The control EC50 of 5MFI was 2.48 μM with Rmax = 1.88 g. In the presence of diazinon, EC50 was 12.45 μM, while Rmax was reduced to 0.43 g. After washing, the EC50 and Rmax values were again closer to the control level (3.80 μM and 1.04 g). Diazinon 1 μM did not inhibit Ascaris suum contractions caused by ACh, but it increased the Rmax. Diazinon in our study exhibits two opposite effects on the motor activity of the ileum. In low nanomolar concentrations the dominat is its effect on AChE and the stimulation of contractions. Furthermore, in concentrations that approach micromolar values diazinon has a direct inhibitory effect on muscarinic receptors. The direct inhibitory effect of diazinon on A. suum contractions was not found.",
journal = "Research in Veterinary Science",
title = "Two opposite dose-dependent effects of diazinon on the motor activity of the rat ileum",
number = "2",
volume = "112",
doi = "10.1016/j.rvsc.2017.01.002",
pages = "18-25"
}

Trailović, S. M., Marjanović, Đ. S., Vidonja Uzelac, T., Milovanović, M.,& Nedeljković Trailović, J.. (2017). Two opposite dose-dependent effects of diazinon on the motor activity of the rat ileum. in Research in Veterinary Science, 112(2), 18-25.
https://doi.org/10.1016/j.rvsc.2017.01.002

Trailović SM, Marjanović ĐS, Vidonja Uzelac T, Milovanović M, Nedeljković Trailović J. Two opposite dose-dependent effects of diazinon on the motor activity of the rat ileum. in Research in Veterinary Science. 2017;112(2):18-25.
doi:10.1016/j.rvsc.2017.01.002 .

Trailović, Saša M., Marjanović, Đorđe S., Vidonja Uzelac, Teodora, Milovanović, Mirjana, Nedeljković Trailović, Jelena, "Two opposite dose-dependent effects of diazinon on the motor activity of the rat ileum" in Research in Veterinary Science, 112, no. 2 (2017):18-25,
https://doi.org/10.1016/j.rvsc.2017.01.002 . .

TY  - CONF
AU  - Tatalović, Nikola
AU  - Vidonja Uzelac, Teodora
AU  - Mijušković, Ana
AU  - Nikolić-Kokić, Aleksandra
AU  - Oreščanin Dušić, Zorana
AU  - Spasić, Mihajlo
AU  - Paškulin, Roman
AU  - Blagojević, Duško
PY  - 2016
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4203
AB  - The anti-addiction agent ibogaine, prepared from the root of the shrub Tabernanthe iboga and used for the treatment of acute substance abuse, accomplishes its biological effects through interactions with different types of neural transmitter receptors. Ibogaine treatments are sometimes followed by sudden cardiac arrest with a fatal outcome. Ibogaine strongly influences cellular energy, redox state and antioxidant capacity in a dose- and time-dependent manner. Ibogaine application leads to a decrease in cellular ATP level and an increase in CO2 production in the first hour of exposure, followed by increased cellular respiration and production of reactive oxygen species (ROS) which change redox homeostasis after 5 h. It has been proposed that the systemic effect of ibogaine is redox-mediated. In this work, male and female 3 month-old-rats were treated per os with a single dose of either 1 or 20 mg/kg body weight (b.w.) of ibogaine. The activities of antioxidant enzymes: superoxide dismutases 1 and 2 (SOD1 and SOD2, respectively), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S transferase (GST) were measured in the liver, heart and erythrocytes 6 and 24 h after treatment. The treatment with ibogaine did not affect the levels of antioxidants in the liver and erythrocytes in both males and females. However, in males treated with ibogaine, the dose of 1 mg/kg b.w. elevated cardiac MnSOD activity 6 h after administration and lowered it after 24 h. On the other hand, the 20 mg/kg b.w. dose of ibogaine lowered MnSOD and GR activities in the heart 6 and 24 h after administration. In females treated with 20 mg/kg b.w. ibogaine, cardiac SOD and GR activities were lowered. These results suggest that an ibogaine-induced disturbance of ROS homeostasis in the heart is one reason why the heart is more prone to sudden functional disruption and arrest.
PB  - Bratislava, Slovak Republic: Institute of Normal and Pathological Physiology, Slovak Academy of Sciences in cooperation with NO club
C3  - 2nd Joint Meeting of Slovak and Serbian Physiological Societies “Physiology Without Frontiers“, Book of Abstracts
T1  - Ibogaine affects the redox status in rat heart
SP  - 56
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4203
ER  - 

@conference{
author = "Tatalović, Nikola and Vidonja Uzelac, Teodora and Mijušković, Ana and Nikolić-Kokić, Aleksandra and Oreščanin Dušić, Zorana and Spasić, Mihajlo and Paškulin, Roman and Blagojević, Duško",
year = "2016",
abstract = "The anti-addiction agent ibogaine, prepared from the root of the shrub Tabernanthe iboga and used for the treatment of acute substance abuse, accomplishes its biological effects through interactions with different types of neural transmitter receptors. Ibogaine treatments are sometimes followed by sudden cardiac arrest with a fatal outcome. Ibogaine strongly influences cellular energy, redox state and antioxidant capacity in a dose- and time-dependent manner. Ibogaine application leads to a decrease in cellular ATP level and an increase in CO2 production in the first hour of exposure, followed by increased cellular respiration and production of reactive oxygen species (ROS) which change redox homeostasis after 5 h. It has been proposed that the systemic effect of ibogaine is redox-mediated. In this work, male and female 3 month-old-rats were treated per os with a single dose of either 1 or 20 mg/kg body weight (b.w.) of ibogaine. The activities of antioxidant enzymes: superoxide dismutases 1 and 2 (SOD1 and SOD2, respectively), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S transferase (GST) were measured in the liver, heart and erythrocytes 6 and 24 h after treatment. The treatment with ibogaine did not affect the levels of antioxidants in the liver and erythrocytes in both males and females. However, in males treated with ibogaine, the dose of 1 mg/kg b.w. elevated cardiac MnSOD activity 6 h after administration and lowered it after 24 h. On the other hand, the 20 mg/kg b.w. dose of ibogaine lowered MnSOD and GR activities in the heart 6 and 24 h after administration. In females treated with 20 mg/kg b.w. ibogaine, cardiac SOD and GR activities were lowered. These results suggest that an ibogaine-induced disturbance of ROS homeostasis in the heart is one reason why the heart is more prone to sudden functional disruption and arrest.",
publisher = "Bratislava, Slovak Republic: Institute of Normal and Pathological Physiology, Slovak Academy of Sciences in cooperation with NO club",
journal = "2nd Joint Meeting of Slovak and Serbian Physiological Societies “Physiology Without Frontiers“, Book of Abstracts",
title = "Ibogaine affects the redox status in rat heart",
pages = "56",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4203"
}

Tatalović, N., Vidonja Uzelac, T., Mijušković, A., Nikolić-Kokić, A., Oreščanin Dušić, Z., Spasić, M., Paškulin, R.,& Blagojević, D.. (2016). Ibogaine affects the redox status in rat heart. in 2nd Joint Meeting of Slovak and Serbian Physiological Societies “Physiology Without Frontiers“, Book of Abstracts
Bratislava, Slovak Republic: Institute of Normal and Pathological Physiology, Slovak Academy of Sciences in cooperation with NO club., 56.
https://hdl.handle.net/21.15107/rcub_ibiss_4203

Tatalović N, Vidonja Uzelac T, Mijušković A, Nikolić-Kokić A, Oreščanin Dušić Z, Spasić M, Paškulin R, Blagojević D. Ibogaine affects the redox status in rat heart. in 2nd Joint Meeting of Slovak and Serbian Physiological Societies “Physiology Without Frontiers“, Book of Abstracts. 2016;:56.
https://hdl.handle.net/21.15107/rcub_ibiss_4203 .

Tatalović, Nikola, Vidonja Uzelac, Teodora, Mijušković, Ana, Nikolić-Kokić, Aleksandra, Oreščanin Dušić, Zorana, Spasić, Mihajlo, Paškulin, Roman, Blagojević, Duško, "Ibogaine affects the redox status in rat heart" in 2nd Joint Meeting of Slovak and Serbian Physiological Societies “Physiology Without Frontiers“, Book of Abstracts (2016):56,
https://hdl.handle.net/21.15107/rcub_ibiss_4203 .

TY  - JOUR
AU  - Bajčetić, Milica
AU  - Vidonja Uzelac, Teodora
PY  - 2012
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/344
AB  - This paper is focused on the most prominent problems of the contemporary pediatric pharmacotherapy: the lack of pediatrically designed and evaluated drugs, as well as the lack of pediatric formulations for children under 12 years of age. The availability of drugs that can be used in the treatment of children is significantly limited with the lack of pediatric formulations both for oral and parenteral use. Besides that, a majority of drugs that are used in the therapy of neonates and children's are not properly evaluated, so they are used off-label and unlicensed, which significantly influences efficacy and safety of a therapy. In addition, certain excipients that should be pharmacologically inactive can eventually cause severe adverse effects in neonates and infants. The dosing of drugs in formulations that can be used by children, based on results of pediatric clinical studies, is the utmost imperative of the contemporary pediatric pharmacotherapy.
AB  - Ovaj rad je fokusiran na najznačajnije probleme savremene farmakoterapije u pedijatriji: nedostatak pedijatrijski dizajniranih i evaluiranih lekova, kao i nedostatak pedijatrijskih formulacija za decu mlađu od 12 godina. Dostupnost lekova koji se mogu koristiti u terapiji dece značajno je ograničena nedostatkom pedijatrijskih formulacija kako za oralnu tako i za parenteralnu primenu. Osim toga, veliki broj lekova koji se svakodnevno koristi u terapiji novorođene dece nije propisno evaluiran i upotrebljava se najčešće mimo propisane licence, što značajno utiče na efikasnost i bezbednost terapije. Osim toga, pojedine pomoćne supstance, koje u principu treba da budu farmakološki neaktivna jedinjenja, mogu izazvati ozbiljne neželjene efekte kod novorođenčadi i odojčadi. Doziranje lekova u formulacijama koje mogu da koriste deca, zasnovano na rezultatima pedijatrijskih kliničkih studija, imperativ je savremene farmakoterapije dece.
T2  - Arhiv za farmaciju
T1  - Raspoloživost, efikasnost i kvalitet lekova u pedijatriji
T1  - Availability, quality and efficacy of drugs for use in pediatric patients
IS  - 4
VL  - 62
SP  - 279
EP  - 287
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_344
ER  - 

@article{
author = "Bajčetić, Milica and Vidonja Uzelac, Teodora",
year = "2012, 2012",
abstract = "This paper is focused on the most prominent problems of the contemporary pediatric pharmacotherapy: the lack of pediatrically designed and evaluated drugs, as well as the lack of pediatric formulations for children under 12 years of age. The availability of drugs that can be used in the treatment of children is significantly limited with the lack of pediatric formulations both for oral and parenteral use. Besides that, a majority of drugs that are used in the therapy of neonates and children's are not properly evaluated, so they are used off-label and unlicensed, which significantly influences efficacy and safety of a therapy. In addition, certain excipients that should be pharmacologically inactive can eventually cause severe adverse effects in neonates and infants. The dosing of drugs in formulations that can be used by children, based on results of pediatric clinical studies, is the utmost imperative of the contemporary pediatric pharmacotherapy., Ovaj rad je fokusiran na najznačajnije probleme savremene farmakoterapije u pedijatriji: nedostatak pedijatrijski dizajniranih i evaluiranih lekova, kao i nedostatak pedijatrijskih formulacija za decu mlađu od 12 godina. Dostupnost lekova koji se mogu koristiti u terapiji dece značajno je ograničena nedostatkom pedijatrijskih formulacija kako za oralnu tako i za parenteralnu primenu. Osim toga, veliki broj lekova koji se svakodnevno koristi u terapiji novorođene dece nije propisno evaluiran i upotrebljava se najčešće mimo propisane licence, što značajno utiče na efikasnost i bezbednost terapije. Osim toga, pojedine pomoćne supstance, koje u principu treba da budu farmakološki neaktivna jedinjenja, mogu izazvati ozbiljne neželjene efekte kod novorođenčadi i odojčadi. Doziranje lekova u formulacijama koje mogu da koriste deca, zasnovano na rezultatima pedijatrijskih kliničkih studija, imperativ je savremene farmakoterapije dece.",
journal = "Arhiv za farmaciju",
title = "Raspoloživost, efikasnost i kvalitet lekova u pedijatriji, Availability, quality and efficacy of drugs for use in pediatric patients",
number = "4",
volume = "62",
pages = "279-287",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_344"
}

Bajčetić, M.,& Vidonja Uzelac, T.. (2012). Raspoloživost, efikasnost i kvalitet lekova u pedijatriji. in Arhiv za farmaciju, 62(4), 279-287.
https://hdl.handle.net/21.15107/rcub_ibiss_344

Bajčetić M, Vidonja Uzelac T. Raspoloživost, efikasnost i kvalitet lekova u pedijatriji. in Arhiv za farmaciju. 2012;62(4):279-287.
https://hdl.handle.net/21.15107/rcub_ibiss_344 .

Bajčetić, Milica, Vidonja Uzelac, Teodora, "Raspoloživost, efikasnost i kvalitet lekova u pedijatriji" in Arhiv za farmaciju, 62, no. 4 (2012):279-287,
https://hdl.handle.net/21.15107/rcub_ibiss_344 .