Koželj, Gordana

Link to this page

Authority KeyName Variants
468d0578-f8a0-417f-9d1c-bc09440ae7a6
  • Koželj, Gordana (2)
Projects

Author's Bibliography

Ibogaine Has Sex-Specific Plasma Bioavailability, Histopathological and Redox/Antioxidant Effects in Rat Liver and Kidneys: A Study on Females

Tatalović, Nikola; Vidonja Uzelac, Teodora; Mijović, Milica; Koželj, Gordana; Nikolić-Kokić, Aleksandra; Oreščanin Dušić, Zorana; Bresjanac, Mara; Blagojević, Duško

(Basel: MDPI, 2021)

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 . .
2
2

Ibogaine redox potential - the effects on antioxidant enzymes after ingestion

Vidonja Uzelac, Teodora; Tatalović, Nikola; Koželj, Gordana; Oreščanin Dušić, Zorana; Nikolić-Kokić, Aleksandra; Spasić, Mihajlo; Paškulin, Roman; Bresjanac, Maja; Blagojević, Duško

(Belgrade : Faculty of Chemistry, 2017)

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 .