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

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

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

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

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

TY  - JOUR
AU  - Nikolić-Kokić, Aleksandra
AU  - Oreščanin Dušić, Zorana
AU  - Spasojevic, Ivan
AU  - Slavic, Marija
AU  - Mijuskovic, Ana
AU  - Paskulin, Roman
AU  - Miljevic, Cedo
AU  - Spasić, Mihajlo
AU  - Blagojević, Duško
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1970
AB  - Ethnopharmacological relevance: Ibogaine is a naturally occurring
   alkaloid with psychotropic and metabotropic effects, derived from the
   bark of the root of the West African Tabernanthe iboga plant. The tribes
   of Kongo basin have been using iboga as a stimulant, for medicinal
   purposes, and in rite of passage ceremonies, for centuries. Besides, it
   has been found that this drug has anti-addictive effects.
   Aim of the study: Previous studies have demonstrated that ibogaine
   changed the quantity of ATP and energy related enzymes as well as the
   activity of antioxidant enzymes in cells thus altering redox equilibrium
   in a time manner. In this work, the mechanism of its action was further
   studied by measuring the effects of ibogaine in human erythrocytes in
   vitro on ATP liberation, membrane fluidity and antioxidant enzymes
   activity.
   Materials and methods: Heparinized human blood samples were incubated
   with ibogaine (10 and 20 mu M) at 37 degrees C for 1 h. Blood plasma was
   separated by centrifugation and the levels of ATP and uric acid were
   measured 10 mm after the addition of ibogaine using standard kits. The
   activity of copper zinc superoxide dismutase (SOD1), catalase (CAT),
   glutathione peroxidase (GSH-Px) and glutathione reductase (GR) were
   measured in erythrocytes after incubation period. The stability of SOD1
   activity was further tested through in vitro incubation with H2O2 and
   scanning of its electrophoretic profiles. Membrane fluidity was
   determined using an electron paramagnetic resonance spin-labelling
   method.
   Results: Results showed that ibogaine treatment of erythrocytes in vitro
   increased ATP concentration in the blood plasma without changes in
   neither erythrocytes membrane fluidity nor uric acid concentration.
   lbogaine also increased SOD1 activity in erythrocytes at both doses
   applied here. Treatment with 20 mu M also elevated GR activity after in
   vitro incubation at 37 degrees C. Electrophoretic profiles revealed that
   incubation with ibogaine mitigates H2O2 mediated suppression of SOD1
   activity.
   Conclusion: Some of the effects of ibogaine seem to be mediated through
   its influence on energy metabolism, redox active processes and the
   effects of discrete fluctuations of individual reactive oxygen species
   on different levels of enzyme activities. Overall, ibogaine acts as a
   pro-antioxidant by increasing activity of antioxidative enzymes and as
   an adaptagene in oxidative distress. (C) 2015 Published by Elsevier
   Ireland Ltd.
T2  - Journal of Ethnopharmacology
T1  - Ex vivo effects of ibogaine on the activity of antioxidative enzymes in
 human erythrocytes
VL  - 164
DO  - 10.1016/j.jep.2015.01.037
SP  - 64
EP  - 70
ER  - 

@article{
author = "Nikolić-Kokić, Aleksandra and Oreščanin Dušić, Zorana and Spasojevic, Ivan and Slavic, Marija and Mijuskovic, Ana and Paskulin, Roman and Miljevic, Cedo and Spasić, Mihajlo and Blagojević, Duško",
year = "2015",
abstract = "Ethnopharmacological relevance: Ibogaine is a naturally occurring
   alkaloid with psychotropic and metabotropic effects, derived from the
   bark of the root of the West African Tabernanthe iboga plant. The tribes
   of Kongo basin have been using iboga as a stimulant, for medicinal
   purposes, and in rite of passage ceremonies, for centuries. Besides, it
   has been found that this drug has anti-addictive effects.
   Aim of the study: Previous studies have demonstrated that ibogaine
   changed the quantity of ATP and energy related enzymes as well as the
   activity of antioxidant enzymes in cells thus altering redox equilibrium
   in a time manner. In this work, the mechanism of its action was further
   studied by measuring the effects of ibogaine in human erythrocytes in
   vitro on ATP liberation, membrane fluidity and antioxidant enzymes
   activity.
   Materials and methods: Heparinized human blood samples were incubated
   with ibogaine (10 and 20 mu M) at 37 degrees C for 1 h. Blood plasma was
   separated by centrifugation and the levels of ATP and uric acid were
   measured 10 mm after the addition of ibogaine using standard kits. The
   activity of copper zinc superoxide dismutase (SOD1), catalase (CAT),
   glutathione peroxidase (GSH-Px) and glutathione reductase (GR) were
   measured in erythrocytes after incubation period. The stability of SOD1
   activity was further tested through in vitro incubation with H2O2 and
   scanning of its electrophoretic profiles. Membrane fluidity was
   determined using an electron paramagnetic resonance spin-labelling
   method.
   Results: Results showed that ibogaine treatment of erythrocytes in vitro
   increased ATP concentration in the blood plasma without changes in
   neither erythrocytes membrane fluidity nor uric acid concentration.
   lbogaine also increased SOD1 activity in erythrocytes at both doses
   applied here. Treatment with 20 mu M also elevated GR activity after in
   vitro incubation at 37 degrees C. Electrophoretic profiles revealed that
   incubation with ibogaine mitigates H2O2 mediated suppression of SOD1
   activity.
   Conclusion: Some of the effects of ibogaine seem to be mediated through
   its influence on energy metabolism, redox active processes and the
   effects of discrete fluctuations of individual reactive oxygen species
   on different levels of enzyme activities. Overall, ibogaine acts as a
   pro-antioxidant by increasing activity of antioxidative enzymes and as
   an adaptagene in oxidative distress. (C) 2015 Published by Elsevier
   Ireland Ltd.",
journal = "Journal of Ethnopharmacology",
title = "Ex vivo effects of ibogaine on the activity of antioxidative enzymes in
 human erythrocytes",
volume = "164",
doi = "10.1016/j.jep.2015.01.037",
pages = "64-70"
}

Nikolić-Kokić, A., Oreščanin Dušić, Z., Spasojevic, I., Slavic, M., Mijuskovic, A., Paskulin, R., Miljevic, C., Spasić, M.,& Blagojević, D.. (2015). Ex vivo effects of ibogaine on the activity of antioxidative enzymes in
 human erythrocytes. in Journal of Ethnopharmacology, 164, 64-70.
https://doi.org/10.1016/j.jep.2015.01.037

Nikolić-Kokić A, Oreščanin Dušić Z, Spasojevic I, Slavic M, Mijuskovic A, Paskulin R, Miljevic C, Spasić M, Blagojević D. Ex vivo effects of ibogaine on the activity of antioxidative enzymes in
 human erythrocytes. in Journal of Ethnopharmacology. 2015;164:64-70.
doi:10.1016/j.jep.2015.01.037 .

Nikolić-Kokić, Aleksandra, Oreščanin Dušić, Zorana, Spasojevic, Ivan, Slavic, Marija, Mijuskovic, Ana, Paskulin, Roman, Miljevic, Cedo, Spasić, Mihajlo, Blagojević, Duško, "Ex vivo effects of ibogaine on the activity of antioxidative enzymes in
 human erythrocytes" in Journal of Ethnopharmacology, 164 (2015):64-70,
https://doi.org/10.1016/j.jep.2015.01.037 . .