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 .