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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

TY  - JOUR
AU  - 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  - Miljević, Čedo D.
AU  - Nikolić-Kokić, Aleksandra
AU  - Blagojević, Duško
AU  - Milovanović, Maja
AU  - Munjiza, Ana
AU  - Jukić, Marin M
AU  - Pešić, Vesna
AU  - Lečić-Toševski, Dušica
AU  - Spasić, Mihajlo
PY  - 2018
UR  - https://www.sciencedirect.com/science/article/pii/S0165178117323272?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3154
AB  - To determine the relationship between alterations in the activity of the enzymes participating in antioxidative defense system and neurological soft signs (NSS) in schizophrenic patients with the first episode psychosis (SFE, n = 19), patients in relapse (SR, n = 46), and healthy controls (HC, n = 20). NSS intensity and enzymatic plasma activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) were compared between SFE, SR and HC subjects and a follow-up correlation analyses between the enzyme activities and NSS intensity was performed. NSS intensity was increased four times in schizophrenic patients compared with healthy controls. Activities of SOD and CAT were 40% decreased in SFE and these reductions were ameliorated by antipsychotic treatment. GPX activity was 20% decreased in both patient groups compared with controls. A negative correlation between NSS intensity and GPX activity was specifically found in the SFE patients. The data in this report argue that a reduction of GPX activity might be one of the causes for the emergence of NSS at the onset of schizophrenia, and provide the evidence that antipsychotic therapy can attenuate activity reductions of SOD and CAT, but not the activity reduction of GPX and the intensity of NSS.
T2  - Psychiatry research
T1  - Association between neurological soft signs and antioxidant enzyme activity in schizophrenic patients.
VL  - 269
DO  - 10.1016/j.psychres.2018.09.009
SP  - 746
EP  - 752
ER  - 

@article{
author = "Miljević, Čedo D. and Nikolić-Kokić, Aleksandra and Blagojević, Duško and Milovanović, Maja and Munjiza, Ana and Jukić, Marin M and Pešić, Vesna and Lečić-Toševski, Dušica and Spasić, Mihajlo",
year = "2018",
abstract = "To determine the relationship between alterations in the activity of the enzymes participating in antioxidative defense system and neurological soft signs (NSS) in schizophrenic patients with the first episode psychosis (SFE, n = 19), patients in relapse (SR, n = 46), and healthy controls (HC, n = 20). NSS intensity and enzymatic plasma activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) were compared between SFE, SR and HC subjects and a follow-up correlation analyses between the enzyme activities and NSS intensity was performed. NSS intensity was increased four times in schizophrenic patients compared with healthy controls. Activities of SOD and CAT were 40% decreased in SFE and these reductions were ameliorated by antipsychotic treatment. GPX activity was 20% decreased in both patient groups compared with controls. A negative correlation between NSS intensity and GPX activity was specifically found in the SFE patients. The data in this report argue that a reduction of GPX activity might be one of the causes for the emergence of NSS at the onset of schizophrenia, and provide the evidence that antipsychotic therapy can attenuate activity reductions of SOD and CAT, but not the activity reduction of GPX and the intensity of NSS.",
journal = "Psychiatry research",
title = "Association between neurological soft signs and antioxidant enzyme activity in schizophrenic patients.",
volume = "269",
doi = "10.1016/j.psychres.2018.09.009",
pages = "746-752"
}

Miljević, Č. D., Nikolić-Kokić, A., Blagojević, D., Milovanović, M., Munjiza, A., Jukić, M. M., Pešić, V., Lečić-Toševski, D.,& Spasić, M.. (2018). Association between neurological soft signs and antioxidant enzyme activity in schizophrenic patients.. in Psychiatry research, 269, 746-752.
https://doi.org/10.1016/j.psychres.2018.09.009

Miljević ČD, Nikolić-Kokić A, Blagojević D, Milovanović M, Munjiza A, Jukić MM, Pešić V, Lečić-Toševski D, Spasić M. Association between neurological soft signs and antioxidant enzyme activity in schizophrenic patients.. in Psychiatry research. 2018;269:746-752.
doi:10.1016/j.psychres.2018.09.009 .

Miljević, Čedo D., Nikolić-Kokić, Aleksandra, Blagojević, Duško, Milovanović, Maja, Munjiza, Ana, Jukić, Marin M, Pešić, Vesna, Lečić-Toševski, Dušica, Spasić, Mihajlo, "Association between neurological soft signs and antioxidant enzyme activity in schizophrenic patients." in Psychiatry research, 269 (2018):746-752,
https://doi.org/10.1016/j.psychres.2018.09.009 . .

TY  - JOUR
AU  - Nikolić-Kokić, Aleksandra
AU  - Tatalović, Nikola
AU  - Brkljačić, Jelena
AU  - Mijović, Milica
AU  - Mijušković, Ana
AU  - Miler, Marko
AU  - Oreščanin Dušić, Zorana
AU  - Nikolić, Milan
AU  - Milošević, Verica
AU  - Blagojević, Duško
AU  - Spasić, Mihajlo
AU  - Miljević, Čedo
PY  - 2018
UR  - https://www.tandfonline.com/doi/full/10.1080/15287394.2018.1495587
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3121
AB  - Atypical antipsychotics produce severe side effects including myocarditis that may be attributed to oxidative stress. The aim of this study was to investigate the influence of clozapine, ziprasidone, and sertindole on rat heart morphology and determine whether redox imbalane plays a role in development of histopathological changes. Adult 3-month-old male Wistar rats were treated with recommended daily dose for selected drugs. After 4 week treatment histopathological analysis of the heart was performed and expression and activity of antioxidant enzymes determined. All examined drugs induced histopathological changes that were characterized as toxic myocarditis. Degenerative changes in cardiomyocytes were accompanied by lymphocytic infiltration as well as pericardial histopathological alterations in all treated groups. The least prominent changes were observed in sertindole-treated animals, and most severe with clozapine. Clozapine increased superoxide dismutase 1 (SOD1) activity while ziprasidone reduced glutathione reductase (GR) activity. Sertindole exerted no marked effect on antioxidant enzyme function in the heart even though myocardial degeneration was noted. In conclusion, treatment with clozapine or ziprasidone induced pathophysiological alterations in rat heart, which appeared to be associated disturbances in antioxidant capacity. Abbreviation: AAP, Atypical antipsychotics; ROS, reactive oxygen species; SOD1, Copper-zinc superoxide dismutase; SOD2, Manganese superoxide dismutase; CAT, Catalase; GPx, Glutathione peroxidase; GR, Glutathione reductase; H&E, hematoxylin and eosin stain; TNF- α, tumor necrosis factor alpha.
T2  - Journal of Toxicology and Environmental Health, Part A
T1  - Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function
IS  - 17
VL  - 81
DO  - 10.1080/15287394.2018.1495587
SP  - 844
EP  - 853
ER  - 

@article{
author = "Nikolić-Kokić, Aleksandra and Tatalović, Nikola and Brkljačić, Jelena and Mijović, Milica and Mijušković, Ana and Miler, Marko and Oreščanin Dušić, Zorana and Nikolić, Milan and Milošević, Verica and Blagojević, Duško and Spasić, Mihajlo and Miljević, Čedo",
year = "2018",
abstract = "Atypical antipsychotics produce severe side effects including myocarditis that may be attributed to oxidative stress. The aim of this study was to investigate the influence of clozapine, ziprasidone, and sertindole on rat heart morphology and determine whether redox imbalane plays a role in development of histopathological changes. Adult 3-month-old male Wistar rats were treated with recommended daily dose for selected drugs. After 4 week treatment histopathological analysis of the heart was performed and expression and activity of antioxidant enzymes determined. All examined drugs induced histopathological changes that were characterized as toxic myocarditis. Degenerative changes in cardiomyocytes were accompanied by lymphocytic infiltration as well as pericardial histopathological alterations in all treated groups. The least prominent changes were observed in sertindole-treated animals, and most severe with clozapine. Clozapine increased superoxide dismutase 1 (SOD1) activity while ziprasidone reduced glutathione reductase (GR) activity. Sertindole exerted no marked effect on antioxidant enzyme function in the heart even though myocardial degeneration was noted. In conclusion, treatment with clozapine or ziprasidone induced pathophysiological alterations in rat heart, which appeared to be associated disturbances in antioxidant capacity. Abbreviation: AAP, Atypical antipsychotics; ROS, reactive oxygen species; SOD1, Copper-zinc superoxide dismutase; SOD2, Manganese superoxide dismutase; CAT, Catalase; GPx, Glutathione peroxidase; GR, Glutathione reductase; H&E, hematoxylin and eosin stain; TNF- α, tumor necrosis factor alpha.",
journal = "Journal of Toxicology and Environmental Health, Part A",
title = "Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function",
number = "17",
volume = "81",
doi = "10.1080/15287394.2018.1495587",
pages = "844-853"
}

Nikolić-Kokić, A., Tatalović, N., Brkljačić, J., Mijović, M., Mijušković, A., Miler, M., Oreščanin Dušić, Z., Nikolić, M., Milošević, V., Blagojević, D., Spasić, M.,& Miljević, Č.. (2018). Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function. in Journal of Toxicology and Environmental Health, Part A, 81(17), 844-853.
https://doi.org/10.1080/15287394.2018.1495587

Nikolić-Kokić A, Tatalović N, Brkljačić J, Mijović M, Mijušković A, Miler M, Oreščanin Dušić Z, Nikolić M, Milošević V, Blagojević D, Spasić M, Miljević Č. Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function. in Journal of Toxicology and Environmental Health, Part A. 2018;81(17):844-853.
doi:10.1080/15287394.2018.1495587 .

Nikolić-Kokić, Aleksandra, Tatalović, Nikola, Brkljačić, Jelena, Mijović, Milica, Mijušković, Ana, Miler, Marko, Oreščanin Dušić, Zorana, Nikolić, Milan, Milošević, Verica, Blagojević, Duško, Spasić, Mihajlo, Miljević, Čedo, "Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function" in Journal of Toxicology and Environmental Health, Part A, 81, no. 17 (2018):844-853,
https://doi.org/10.1080/15287394.2018.1495587 . .

TY  - JOUR
AU  - Opačić, Miloš
AU  - Stević, Zorica
AU  - Baščarević, Vladimir
AU  - Živić, Miroslav
AU  - Spasić, Mihajlo
AU  - Spasojević, Ivan
PY  - 2018
UR  - http://www.liebertpub.com/doi/10.1089/ars.2017.7433
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3065
AB  - The monitoring of progression in amyotrophic lateral sclerosis (ALS) relies on clinical outcome measures that take months to interpret, such as revised ALS functional rating scale (ALSFRS-R) score, with no approved biomarkers. A number of clinical studies have documented the involvement of oxidative stress in ALS pathology. Pertinent to this, we propose to evaluate oxidation-reduction potential (ORP) of cerebrospinal fluid (CSF) as a potential indicator of ALS progression. The case-control study included 24 patients with neurological non-neurodegenerative disorders (controls) and 82 ALS patients with different degrees of disease (ALSFRS-R score: 21-47). ORP was significantly higher in ALS patients than controls. It was not dependent on age or gender. A strong negative correlation was found between ORP and ALSFRS-R score for all patients and patients with spinal onset. In other words, ORP increased with ALS progression. No correlation was found for the subset of patients with bulbar onset, most likely because of the physical distance between neurodegenerative loci and the site of CSF collection. These results lead to the hypothesis that ORP of CSF has a potential as monitoring biomarker in ALS, particularly in the cohort of patients with spinal onset. Antioxid. Redox Signal. 28, 1570-1575.
T2  - Antioxidants and Redox Signaling
T1  - Can Oxidation-Reduction Potential of Cerebrospinal Fluid Be a Monitoring Biomarker in Amyotrophic Lateral Sclerosis?
IS  - 17
VL  - 28
DO  - 10.1089/ars.2017.7433
SP  - 1570
EP  - 1575
ER  - 

@article{
author = "Opačić, Miloš and Stević, Zorica and Baščarević, Vladimir and Živić, Miroslav and Spasić, Mihajlo and Spasojević, Ivan",
year = "2018",
abstract = "The monitoring of progression in amyotrophic lateral sclerosis (ALS) relies on clinical outcome measures that take months to interpret, such as revised ALS functional rating scale (ALSFRS-R) score, with no approved biomarkers. A number of clinical studies have documented the involvement of oxidative stress in ALS pathology. Pertinent to this, we propose to evaluate oxidation-reduction potential (ORP) of cerebrospinal fluid (CSF) as a potential indicator of ALS progression. The case-control study included 24 patients with neurological non-neurodegenerative disorders (controls) and 82 ALS patients with different degrees of disease (ALSFRS-R score: 21-47). ORP was significantly higher in ALS patients than controls. It was not dependent on age or gender. A strong negative correlation was found between ORP and ALSFRS-R score for all patients and patients with spinal onset. In other words, ORP increased with ALS progression. No correlation was found for the subset of patients with bulbar onset, most likely because of the physical distance between neurodegenerative loci and the site of CSF collection. These results lead to the hypothesis that ORP of CSF has a potential as monitoring biomarker in ALS, particularly in the cohort of patients with spinal onset. Antioxid. Redox Signal. 28, 1570-1575.",
journal = "Antioxidants and Redox Signaling",
title = "Can Oxidation-Reduction Potential of Cerebrospinal Fluid Be a Monitoring Biomarker in Amyotrophic Lateral Sclerosis?",
number = "17",
volume = "28",
doi = "10.1089/ars.2017.7433",
pages = "1570-1575"
}

Opačić, M., Stević, Z., Baščarević, V., Živić, M., Spasić, M.,& Spasojević, I.. (2018). Can Oxidation-Reduction Potential of Cerebrospinal Fluid Be a Monitoring Biomarker in Amyotrophic Lateral Sclerosis?. in Antioxidants and Redox Signaling, 28(17), 1570-1575.
https://doi.org/10.1089/ars.2017.7433

Opačić M, Stević Z, Baščarević V, Živić M, Spasić M, Spasojević I. Can Oxidation-Reduction Potential of Cerebrospinal Fluid Be a Monitoring Biomarker in Amyotrophic Lateral Sclerosis?. in Antioxidants and Redox Signaling. 2018;28(17):1570-1575.
doi:10.1089/ars.2017.7433 .

Opačić, Miloš, Stević, Zorica, Baščarević, Vladimir, Živić, Miroslav, Spasić, Mihajlo, Spasojević, Ivan, "Can Oxidation-Reduction Potential of Cerebrospinal Fluid Be a Monitoring Biomarker in Amyotrophic Lateral Sclerosis?" in Antioxidants and Redox Signaling, 28, no. 17 (2018):1570-1575,
https://doi.org/10.1089/ars.2017.7433 . .

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  - Martinov, Jelena
AU  - Krstić, Miodrag
AU  - Spasić, Snežana
AU  - Miletić, Srdjan
AU  - Stefanović-Kojić, Jovana
AU  - Nikolić-Kokić, Aleksandra
AU  - Blagojević, Duško
AU  - Spasojević, Ivan
AU  - Spasić, Mihajlo
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0963996917304787
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2843
AB  - Pectin is the main soluble fiber in apples or citruses. It may be fermented by gut microbiota to metabolites showing local intestinal and systemic effects. A wide range of beneficial effects of dietary pectin includes impacts on the redox milieu and microbiota profile. We prepared pectin-derived oligosaccharides (apple (APDO) and citrus) and polygalacturonic acid-derived oligosaccharides, using alkaline hydrolysis by hydrogen peroxide, and analyzed them by Fourier Transform Infrared spectrometry. Furthermore, we analyzed the effects of pectin-derived oligosaccharides on hydroxyl radical (HO)-generating Fenton reaction using electron paramagnetic resonance spin-trapping spectroscopy, and the effects on the growth of Escherichia coli and Staphylococcus aureus in the presence of dietary-relevant HO-generating system (iron+ascorbate). The oligosaccharides react with HO radical to produce carbon dioxide radical anion (CO 2 - ). A comparative analysis showed that APDO has the most prominent bacteriostatic effect. This might be at least partially related to the higher capacity of APDO to produce CO 2 - , which specifically targets proteins and appears to have a longer lifetime and larger diffusion radius in biological systems compared to HO.
T2  - Food Research International
T1  - Apple pectin-derived oligosaccharides produce carbon dioxide radical anion in Fenton reaction and prevent growth of Escherichia coli and Staphylococcus aureus
DO  - 10.1016/j.foodres.2017.08.040
ER  - 

@article{
author = "Martinov, Jelena and Krstić, Miodrag and Spasić, Snežana and Miletić, Srdjan and Stefanović-Kojić, Jovana and Nikolić-Kokić, Aleksandra and Blagojević, Duško and Spasojević, Ivan and Spasić, Mihajlo",
year = "2017",
abstract = "Pectin is the main soluble fiber in apples or citruses. It may be fermented by gut microbiota to metabolites showing local intestinal and systemic effects. A wide range of beneficial effects of dietary pectin includes impacts on the redox milieu and microbiota profile. We prepared pectin-derived oligosaccharides (apple (APDO) and citrus) and polygalacturonic acid-derived oligosaccharides, using alkaline hydrolysis by hydrogen peroxide, and analyzed them by Fourier Transform Infrared spectrometry. Furthermore, we analyzed the effects of pectin-derived oligosaccharides on hydroxyl radical (HO)-generating Fenton reaction using electron paramagnetic resonance spin-trapping spectroscopy, and the effects on the growth of Escherichia coli and Staphylococcus aureus in the presence of dietary-relevant HO-generating system (iron+ascorbate). The oligosaccharides react with HO radical to produce carbon dioxide radical anion (CO 2 - ). A comparative analysis showed that APDO has the most prominent bacteriostatic effect. This might be at least partially related to the higher capacity of APDO to produce CO 2 - , which specifically targets proteins and appears to have a longer lifetime and larger diffusion radius in biological systems compared to HO.",
journal = "Food Research International",
title = "Apple pectin-derived oligosaccharides produce carbon dioxide radical anion in Fenton reaction and prevent growth of Escherichia coli and Staphylococcus aureus",
doi = "10.1016/j.foodres.2017.08.040"
}

Martinov, J., Krstić, M., Spasić, S., Miletić, S., Stefanović-Kojić, J., Nikolić-Kokić, A., Blagojević, D., Spasojević, I.,& Spasić, M.. (2017). Apple pectin-derived oligosaccharides produce carbon dioxide radical anion in Fenton reaction and prevent growth of Escherichia coli and Staphylococcus aureus. in Food Research International.
https://doi.org/10.1016/j.foodres.2017.08.040

Martinov J, Krstić M, Spasić S, Miletić S, Stefanović-Kojić J, Nikolić-Kokić A, Blagojević D, Spasojević I, Spasić M. Apple pectin-derived oligosaccharides produce carbon dioxide radical anion in Fenton reaction and prevent growth of Escherichia coli and Staphylococcus aureus. in Food Research International. 2017;.
doi:10.1016/j.foodres.2017.08.040 .

Martinov, Jelena, Krstić, Miodrag, Spasić, Snežana, Miletić, Srdjan, Stefanović-Kojić, Jovana, Nikolić-Kokić, Aleksandra, Blagojević, Duško, Spasojević, Ivan, Spasić, Mihajlo, "Apple pectin-derived oligosaccharides produce carbon dioxide radical anion in Fenton reaction and prevent growth of Escherichia coli and Staphylococcus aureus" in Food Research International (2017),
https://doi.org/10.1016/j.foodres.2017.08.040 . .

TY  - JOUR
AU  - Nikolić-Kokić, Aleksandra
AU  - Marinković, Dragan
AU  - Perić, Stojan
AU  - Stević, Zorica
AU  - Spasić, Mihajlo
AU  - Blagojević, Duško
AU  - Rakočević Stojanović, Vidosava
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6358
AB  - Objectives: The aim of our study was to determine if redox imbalance caused by the activities of antioxidant
enzymes existed in erythrocytes of type 1 myotonic dystrophy (DM1) patients.
Methods: The activities of erythrocyte superoxide dismutase, catalase, glutathione peroxidase, and
glutathione reductase were measured in 30 DM1 patients and 15 healthy controls (HCs). The obtained
values were correlated with the Muscular Impairment Rating Scale (MIRS) score and creatine kinase (CK).
Results: Superoxide dismutase and catalase activities were lower in DM1 patients compared to HCs. A
positive correlation was found between disease duration and MIRS score as well as with glutathione
reductase activity. In DM1 patients, there were positive correlations between catalase, glutathione
peroxidase, and glutathione reductase activities. After sub-dividing DM1 patients according to CK levels,
superoxide dismutase activity was still statistically different from HCs. However, catalase activity was
significantly lower only in DM1 patients with increased CK.
Discussion: Undesirable alterations in antioxidant enzyme activities during DM1 disease progression may
result in conditions favoring oxidative stress and changes in metabolism which together could contribute
to muscle wasting.
PB  - Abingdon: Taylor and Francis
T2  - Redox Report
T1  - Redox imbalance in peripheral blood of type 1 myotonic dystrophy patients
IS  - 5
VL  - 21
DO  - 10.1080/13510002.2015.1107311
SP  - 232
EP  - 237
ER  - 

@article{
author = "Nikolić-Kokić, Aleksandra and Marinković, Dragan and Perić, Stojan and Stević, Zorica and Spasić, Mihajlo and Blagojević, Duško and Rakočević Stojanović, Vidosava",
year = "2016",
abstract = "Objectives: The aim of our study was to determine if redox imbalance caused by the activities of antioxidant
enzymes existed in erythrocytes of type 1 myotonic dystrophy (DM1) patients.
Methods: The activities of erythrocyte superoxide dismutase, catalase, glutathione peroxidase, and
glutathione reductase were measured in 30 DM1 patients and 15 healthy controls (HCs). The obtained
values were correlated with the Muscular Impairment Rating Scale (MIRS) score and creatine kinase (CK).
Results: Superoxide dismutase and catalase activities were lower in DM1 patients compared to HCs. A
positive correlation was found between disease duration and MIRS score as well as with glutathione
reductase activity. In DM1 patients, there were positive correlations between catalase, glutathione
peroxidase, and glutathione reductase activities. After sub-dividing DM1 patients according to CK levels,
superoxide dismutase activity was still statistically different from HCs. However, catalase activity was
significantly lower only in DM1 patients with increased CK.
Discussion: Undesirable alterations in antioxidant enzyme activities during DM1 disease progression may
result in conditions favoring oxidative stress and changes in metabolism which together could contribute
to muscle wasting.",
publisher = "Abingdon: Taylor and Francis",
journal = "Redox Report",
title = "Redox imbalance in peripheral blood of type 1 myotonic dystrophy patients",
number = "5",
volume = "21",
doi = "10.1080/13510002.2015.1107311",
pages = "232-237"
}

Nikolić-Kokić, A., Marinković, D., Perić, S., Stević, Z., Spasić, M., Blagojević, D.,& Rakočević Stojanović, V.. (2016). Redox imbalance in peripheral blood of type 1 myotonic dystrophy patients. in Redox Report
Abingdon: Taylor and Francis., 21(5), 232-237.
https://doi.org/10.1080/13510002.2015.1107311

Nikolić-Kokić A, Marinković D, Perić S, Stević Z, Spasić M, Blagojević D, Rakočević Stojanović V. Redox imbalance in peripheral blood of type 1 myotonic dystrophy patients. in Redox Report. 2016;21(5):232-237.
doi:10.1080/13510002.2015.1107311 .

Nikolić-Kokić, Aleksandra, Marinković, Dragan, Perić, Stojan, Stević, Zorica, Spasić, Mihajlo, Blagojević, Duško, Rakočević Stojanović, Vidosava, "Redox imbalance in peripheral blood of type 1 myotonic dystrophy patients" in Redox Report, 21, no. 5 (2016):232-237,
https://doi.org/10.1080/13510002.2015.1107311 . .

TY  - JOUR
AU  - Nikolić-Kokić, Aleksandra
AU  - Mijušković, Ana
AU  - Tatalović, Nikola
AU  - Brkljačić, Jelena
AU  - Miler, Marko
AU  - Oreščanin Dušić, Zorana
AU  - Nikolić, Milan
AU  - Milošević, Verica
AU  - Blagojević, Duško
AU  - Spasić, Mihajlo
AU  - Miljević, Čedo
PY  - 2016
UR  - https://radar.ibiss.bg.ac.rs/123456789/3900
AB  - The use of atypical antipsychotic drugs (APD) was reported to be associated with adverse effects
on the kidneys. Thus, the aim of this study was to examine whether APD exerted their adverse
effects by interfering with the renal antioxidant defense system. Male 3-mo-old Wistar rats were
treated for 28 d with ziprasidone (ZIP), clozapine (CLO), or sertindole (SER) using a daily dose
recommended for antipsychotic drug therapy. The expression and activities of antioxidant
enzymes superoxide dismutase (SOD) type 1 and type 2, catalase (CAT), glutathione reductase
(GR), and glutathione S-transferases (GSTs) activity were measured in the kidneys. Changes in the
kidneys were also evaluated histologically. Ziprasidone, CLO, and SER reduced renal SOD type 1
and type 2 activities. Decreased CAT activity was observed only in SER-treated rats. An inhibition
in GR activity and increased activity of GST was found only after treatment with CLO. Histological
analysis showed dilatation of proximal tubules in kidneys with all three drugs. In conclusion, data
indicate that redox disturbances may contribute to renal morphologic alterations in proximal
tubules in rats treated with all APD.
PB  - Taylor & Francis
T2  - Journal of Toxicology and Environmental Health, Part A: Current Issues
T1  - Effects of antipsychotic drug administration on antioxidative defense enzymes in male rat kidney
IS  - 20
VL  - 79
DO  - 10.1080/15287394.2016.1201706
SP  - 905
EP  - 911
ER  - 

@article{
author = "Nikolić-Kokić, Aleksandra and Mijušković, Ana and Tatalović, Nikola and Brkljačić, Jelena and Miler, Marko and Oreščanin Dušić, Zorana and Nikolić, Milan and Milošević, Verica and Blagojević, Duško and Spasić, Mihajlo and Miljević, Čedo",
year = "2016",
abstract = "The use of atypical antipsychotic drugs (APD) was reported to be associated with adverse effects
on the kidneys. Thus, the aim of this study was to examine whether APD exerted their adverse
effects by interfering with the renal antioxidant defense system. Male 3-mo-old Wistar rats were
treated for 28 d with ziprasidone (ZIP), clozapine (CLO), or sertindole (SER) using a daily dose
recommended for antipsychotic drug therapy. The expression and activities of antioxidant
enzymes superoxide dismutase (SOD) type 1 and type 2, catalase (CAT), glutathione reductase
(GR), and glutathione S-transferases (GSTs) activity were measured in the kidneys. Changes in the
kidneys were also evaluated histologically. Ziprasidone, CLO, and SER reduced renal SOD type 1
and type 2 activities. Decreased CAT activity was observed only in SER-treated rats. An inhibition
in GR activity and increased activity of GST was found only after treatment with CLO. Histological
analysis showed dilatation of proximal tubules in kidneys with all three drugs. In conclusion, data
indicate that redox disturbances may contribute to renal morphologic alterations in proximal
tubules in rats treated with all APD.",
publisher = "Taylor & Francis",
journal = "Journal of Toxicology and Environmental Health, Part A: Current Issues",
title = "Effects of antipsychotic drug administration on antioxidative defense enzymes in male rat kidney",
number = "20",
volume = "79",
doi = "10.1080/15287394.2016.1201706",
pages = "905-911"
}

Nikolić-Kokić, A., Mijušković, A., Tatalović, N., Brkljačić, J., Miler, M., Oreščanin Dušić, Z., Nikolić, M., Milošević, V., Blagojević, D., Spasić, M.,& Miljević, Č.. (2016). Effects of antipsychotic drug administration on antioxidative defense enzymes in male rat kidney. in Journal of Toxicology and Environmental Health, Part A: Current Issues
Taylor & Francis., 79(20), 905-911.
https://doi.org/10.1080/15287394.2016.1201706

Nikolić-Kokić A, Mijušković A, Tatalović N, Brkljačić J, Miler M, Oreščanin Dušić Z, Nikolić M, Milošević V, Blagojević D, Spasić M, Miljević Č. Effects of antipsychotic drug administration on antioxidative defense enzymes in male rat kidney. in Journal of Toxicology and Environmental Health, Part A: Current Issues. 2016;79(20):905-911.
doi:10.1080/15287394.2016.1201706 .

Nikolić-Kokić, Aleksandra, Mijušković, Ana, Tatalović, Nikola, Brkljačić, Jelena, Miler, Marko, Oreščanin Dušić, Zorana, Nikolić, Milan, Milošević, Verica, Blagojević, Duško, Spasić, Mihajlo, Miljević, Čedo, "Effects of antipsychotic drug administration on antioxidative defense enzymes in male rat kidney" in Journal of Toxicology and Environmental Health, Part A: Current Issues, 79, no. 20 (2016):905-911,
https://doi.org/10.1080/15287394.2016.1201706 . .

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  - CONF
AU  - Mijuskovic, Ana
AU  - Tatalovic, Nikola
AU  - Oreščanin Dušić, Zorana
AU  - Nikolić-Kokić, Aleksandra
AU  - Spasić, Mihajlo
AU  - Blagojević, Duško
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1966
C3  - Nitric Oxide-Biology and Chemistry
T1  - Hydrogen sulphide mediated uterine relaxation is not altered by elevated
 homocysteine
VL  - 47
DO  - 10.1016/j.niox.2015.02.080
ER  - 

@conference{
author = "Mijuskovic, Ana and Tatalovic, Nikola and Oreščanin Dušić, Zorana and Nikolić-Kokić, Aleksandra and Spasić, Mihajlo and Blagojević, Duško",
year = "2015",
journal = "Nitric Oxide-Biology and Chemistry",
title = "Hydrogen sulphide mediated uterine relaxation is not altered by elevated
 homocysteine",
volume = "47",
doi = "10.1016/j.niox.2015.02.080"
}

Mijuskovic, A., Tatalovic, N., Oreščanin Dušić, Z., Nikolić-Kokić, A., Spasić, M.,& Blagojević, D.. (2015). Hydrogen sulphide mediated uterine relaxation is not altered by elevated
 homocysteine. in Nitric Oxide-Biology and Chemistry, 47.
https://doi.org/10.1016/j.niox.2015.02.080

Mijuskovic A, Tatalovic N, Oreščanin Dušić Z, Nikolić-Kokić A, Spasić M, Blagojević D. Hydrogen sulphide mediated uterine relaxation is not altered by elevated
 homocysteine. in Nitric Oxide-Biology and Chemistry. 2015;47.
doi:10.1016/j.niox.2015.02.080 .

Mijuskovic, Ana, Tatalovic, Nikola, Oreščanin Dušić, Zorana, Nikolić-Kokić, Aleksandra, Spasić, Mihajlo, Blagojević, Duško, "Hydrogen sulphide mediated uterine relaxation is not altered by elevated
 homocysteine" in Nitric Oxide-Biology and Chemistry, 47 (2015),
https://doi.org/10.1016/j.niox.2015.02.080 . .

TY  - JOUR
AU  - Nikolić-Kokić, Aleksandra
AU  - Oreščanin-Dušić, Zorana
AU  - Spasojević, Ivan
AU  - Blagojević, Duško
AU  - Stević, Zorica
AU  - Anđus, Pavle
AU  - Spasić, Mihajlo
PY  - 2015
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6080
AB  - In this work we compared the mutated liver copper zinc-containing superoxide dismutase (SOD1) protein G93A of the transgenic rat model of familial amyotrophic lateral sclerosis (FALS), to wild-type (WT) rat SOD1. We examined their enzymatic activities and effects on isometric contractions of uteri of healthy virgin rats. G93A SOD1 showed a slightly higher activity than WT SOD1 and, in contrast to WT SOD1, G93A SOD1 did not induce smooth muscle relaxation. This result indicates that effects on smooth muscles are not related to SOD1 enzyme activity and suggest that heterodimers of G93A SOD1 form an ion-conducting pore that diminishes the relaxatory effects of SOD1. We propose that this type of pathogenic feedback affects neurons in FALS.
PB  - Belgrade: Serbian Biological Society
T2  - Archives of Biological Sciences
T1  - The Effects of Wild-Type and Mutant SOD1 on Smooth Muscle Contraction
IS  - 1
VL  - 67
DO  - 10.2298/ABS141006023N
SP  - 187
EP  - 192
ER  - 

@article{
author = "Nikolić-Kokić, Aleksandra and Oreščanin-Dušić, Zorana and Spasojević, Ivan and Blagojević, Duško and Stević, Zorica and Anđus, Pavle and Spasić, Mihajlo",
year = "2015",
abstract = "In this work we compared the mutated liver copper zinc-containing superoxide dismutase (SOD1) protein G93A of the transgenic rat model of familial amyotrophic lateral sclerosis (FALS), to wild-type (WT) rat SOD1. We examined their enzymatic activities and effects on isometric contractions of uteri of healthy virgin rats. G93A SOD1 showed a slightly higher activity than WT SOD1 and, in contrast to WT SOD1, G93A SOD1 did not induce smooth muscle relaxation. This result indicates that effects on smooth muscles are not related to SOD1 enzyme activity and suggest that heterodimers of G93A SOD1 form an ion-conducting pore that diminishes the relaxatory effects of SOD1. We propose that this type of pathogenic feedback affects neurons in FALS.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Archives of Biological Sciences",
title = "The Effects of Wild-Type and Mutant SOD1 on Smooth Muscle Contraction",
number = "1",
volume = "67",
doi = "10.2298/ABS141006023N",
pages = "187-192"
}

Nikolić-Kokić, A., Oreščanin-Dušić, Z., Spasojević, I., Blagojević, D., Stević, Z., Anđus, P.,& Spasić, M.. (2015). The Effects of Wild-Type and Mutant SOD1 on Smooth Muscle Contraction. in Archives of Biological Sciences
Belgrade: Serbian Biological Society., 67(1), 187-192.
https://doi.org/10.2298/ABS141006023N

Nikolić-Kokić A, Oreščanin-Dušić Z, Spasojević I, Blagojević D, Stević Z, Anđus P, Spasić M. The Effects of Wild-Type and Mutant SOD1 on Smooth Muscle Contraction. in Archives of Biological Sciences. 2015;67(1):187-192.
doi:10.2298/ABS141006023N .

Nikolić-Kokić, Aleksandra, Oreščanin-Dušić, Zorana, Spasojević, Ivan, Blagojević, Duško, Stević, Zorica, Anđus, Pavle, Spasić, Mihajlo, "The Effects of Wild-Type and Mutant SOD1 on Smooth Muscle Contraction" in Archives of Biological Sciences, 67, no. 1 (2015):187-192,
https://doi.org/10.2298/ABS141006023N . .

TY  - JOUR
AU  - Mijušković, Ana
AU  - Nikolić-Kokić, Aleksandra
AU  - Oreščanin-Dušić, Zorana
AU  - Slavić, Marija
AU  - Spasić, Mihajlo
AU  - Blagojević, Duško
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1934
AB  - Background and PurposeHydrogen sulphide reduces uterine contractility
   and is of potential interest as a treatment for uterine disorders. The
   aim of this study was to explore the mechanism of sodium sulphide
   (Na2S)-induced relaxation of rat uterus, investigate the importance of
   redox effects and ion channel-mediated mechanisms, and any interactions
   between these two mechanisms.
   Experimental ApproachOrgan bath studies were employed to assess the
   pharmacological effects of Na2S in uterine strips by exposing them to
   Na2S with or without Cl- channel blockers (DIDS, NFA, IAA-94,
   T16Ainh-A01, TA), raised KCl (15 and 75mM), K+ channel inhibitors
   (glibenclamide, TEA, 4-AP), L-type Ca2+ channel activator (S-Bay K
   8644), propranolol and methylene blue. The activities of antioxidant
   enzymes were measured in homogenates of treated uteri. The expression of
   bestrophin channel 1 (BEST-1) was determined by Western blotting and
   RT-PCR.
   Key ResultsNa(2)S caused concentration-dependent reversible relaxation
   of spontaneously active and calcium-treated uteri, affecting both
   amplitude and frequency of contractions. Uteri exposed to 75mM KCl were
   less sensitive to Na2S compared with uteri in 15mM KCl. Na2S-induced
   relaxations were abolished by DIDS, but unaffected by other modulators
   or by the absence of extracellular HCO3-, suggesting the involvement of
   chloride ion channels. Na2S in combination with different modulators
   provoked specific changes in the anti-oxidant profiles of uteri. The
   expression of BEST-1, both mRNA and protein, was demonstrated in rat
   uteri.
   Conclusions and ImplicationsThe relaxant effects of Na2S in rat uteri
   are mediated mainly via a DIDS-sensitive Cl--pathway. Components of the
   relaxation are redox- and Ca2+-dependent.
T2  - British Journal of Pharmacology
T1  - Chloride channels mediate sodium sulphide-induced relaxation in rat
 uteri
IS  - 14, SI
VL  - 172
DO  - 10.1111/bph.13161
SP  - 3671
EP  - 3686
ER  - 

@article{
author = "Mijušković, Ana and Nikolić-Kokić, Aleksandra and Oreščanin-Dušić, Zorana and Slavić, Marija and Spasić, Mihajlo and Blagojević, Duško",
year = "2015",
abstract = "Background and PurposeHydrogen sulphide reduces uterine contractility
   and is of potential interest as a treatment for uterine disorders. The
   aim of this study was to explore the mechanism of sodium sulphide
   (Na2S)-induced relaxation of rat uterus, investigate the importance of
   redox effects and ion channel-mediated mechanisms, and any interactions
   between these two mechanisms.
   Experimental ApproachOrgan bath studies were employed to assess the
   pharmacological effects of Na2S in uterine strips by exposing them to
   Na2S with or without Cl- channel blockers (DIDS, NFA, IAA-94,
   T16Ainh-A01, TA), raised KCl (15 and 75mM), K+ channel inhibitors
   (glibenclamide, TEA, 4-AP), L-type Ca2+ channel activator (S-Bay K
   8644), propranolol and methylene blue. The activities of antioxidant
   enzymes were measured in homogenates of treated uteri. The expression of
   bestrophin channel 1 (BEST-1) was determined by Western blotting and
   RT-PCR.
   Key ResultsNa(2)S caused concentration-dependent reversible relaxation
   of spontaneously active and calcium-treated uteri, affecting both
   amplitude and frequency of contractions. Uteri exposed to 75mM KCl were
   less sensitive to Na2S compared with uteri in 15mM KCl. Na2S-induced
   relaxations were abolished by DIDS, but unaffected by other modulators
   or by the absence of extracellular HCO3-, suggesting the involvement of
   chloride ion channels. Na2S in combination with different modulators
   provoked specific changes in the anti-oxidant profiles of uteri. The
   expression of BEST-1, both mRNA and protein, was demonstrated in rat
   uteri.
   Conclusions and ImplicationsThe relaxant effects of Na2S in rat uteri
   are mediated mainly via a DIDS-sensitive Cl--pathway. Components of the
   relaxation are redox- and Ca2+-dependent.",
journal = "British Journal of Pharmacology",
title = "Chloride channels mediate sodium sulphide-induced relaxation in rat
 uteri",
number = "14, SI",
volume = "172",
doi = "10.1111/bph.13161",
pages = "3671-3686"
}

Mijušković, A., Nikolić-Kokić, A., Oreščanin-Dušić, Z., Slavić, M., Spasić, M.,& Blagojević, D.. (2015). Chloride channels mediate sodium sulphide-induced relaxation in rat
 uteri. in British Journal of Pharmacology, 172(14, SI), 3671-3686.
https://doi.org/10.1111/bph.13161

Mijušković A, Nikolić-Kokić A, Oreščanin-Dušić Z, Slavić M, Spasić M, Blagojević D. Chloride channels mediate sodium sulphide-induced relaxation in rat
 uteri. in British Journal of Pharmacology. 2015;172(14, SI):3671-3686.
doi:10.1111/bph.13161 .

Mijušković, Ana, Nikolić-Kokić, Aleksandra, Oreščanin-Dušić, Zorana, Slavić, Marija, Spasić, Mihajlo, Blagojević, Duško, "Chloride channels mediate sodium sulphide-induced relaxation in rat
 uteri" in British Journal of Pharmacology, 172, no. 14, SI (2015):3671-3686,
https://doi.org/10.1111/bph.13161 . .

TY  - CONF
AU  - Tatalović, Nikola
AU  - Bajrica, Mina
AU  - Mijušković, Ana
AU  - Oreščanin Dušić, Zorana
AU  - Nikolić-Kokić, Aleksandra
AU  - Spasić, Mihajlo
AU  - Blagojević, Duško
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4202
AB  - Ibogaine is a naturally occurring alkaloid isolated from the bark of the roots of the West African Tabernanthe iboga plant. It’s well known for its anti-addictive effects. On the other hand, pharmacology is quite complex, affecting 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). Based on our previous study showing ibogaine effects on ATP liberation (127 pM) from erythrocites in vitro, we wanted to investigate direct pharmacological ibogaine effects on aorta and mesenteric artery and to compare them with effects of ATP. Its effects were tested by isolated organ bath studies using aorta and mesenteric artery rings (with and without endothelium) isolated from Wistar rats. Aortic and mesenteric artery rings were precontracted with phenylephrine (10 µM). Ibogaine (64.4 µM) produced a relaxation in the aortic as well as in mesenteric artery rings, in a similar way. Realaxation effects were followed in time (5, 10, 20, 30, and 60 minutes) and it was shown that ibogaine effects are time-dependent. In addition, ibogaine effects are also endothelium dependent since presence of endothelium facilitated relaxation. ATP (127 pM) induced relaxation in the aortic as well as in mesenteric artery rings, and this effect is completely endothelium dependent. Taken together these findings suggest that ibogaine affect smooth muscles directly. Additionally, relaxation is endothelium dependent (possibly is mediated via nitric oxide) and ATP-mediated.
PB  - Ljubljana, Slovenia: Slovenian Biochemical Society
C3  - FEBS3+ Meeting, Molecules of Life, Book of Abstracts
T1  - Ibogaine relaxes rat arteries: the role of endothelium
SP  - 194
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4202
ER  - 

@conference{
author = "Tatalović, Nikola and Bajrica, Mina and Mijušković, Ana and Oreščanin Dušić, Zorana and Nikolić-Kokić, Aleksandra and Spasić, Mihajlo and Blagojević, Duško",
year = "2015",
abstract = "Ibogaine is a naturally occurring alkaloid isolated from the bark of the roots of the West African Tabernanthe iboga plant. It’s well known for its anti-addictive effects. On the other hand, pharmacology is quite complex, affecting 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). Based on our previous study showing ibogaine effects on ATP liberation (127 pM) from erythrocites in vitro, we wanted to investigate direct pharmacological ibogaine effects on aorta and mesenteric artery and to compare them with effects of ATP. Its effects were tested by isolated organ bath studies using aorta and mesenteric artery rings (with and without endothelium) isolated from Wistar rats. Aortic and mesenteric artery rings were precontracted with phenylephrine (10 µM). Ibogaine (64.4 µM) produced a relaxation in the aortic as well as in mesenteric artery rings, in a similar way. Realaxation effects were followed in time (5, 10, 20, 30, and 60 minutes) and it was shown that ibogaine effects are time-dependent. In addition, ibogaine effects are also endothelium dependent since presence of endothelium facilitated relaxation. ATP (127 pM) induced relaxation in the aortic as well as in mesenteric artery rings, and this effect is completely endothelium dependent. Taken together these findings suggest that ibogaine affect smooth muscles directly. Additionally, relaxation is endothelium dependent (possibly is mediated via nitric oxide) and ATP-mediated.",
publisher = "Ljubljana, Slovenia: Slovenian Biochemical Society",
journal = "FEBS3+ Meeting, Molecules of Life, Book of Abstracts",
title = "Ibogaine relaxes rat arteries: the role of endothelium",
pages = "194",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4202"
}

Tatalović, N., Bajrica, M., Mijušković, A., Oreščanin Dušić, Z., Nikolić-Kokić, A., Spasić, M.,& Blagojević, D.. (2015). Ibogaine relaxes rat arteries: the role of endothelium. in FEBS3+ Meeting, Molecules of Life, Book of Abstracts
Ljubljana, Slovenia: Slovenian Biochemical Society., 194.
https://hdl.handle.net/21.15107/rcub_ibiss_4202

Tatalović N, Bajrica M, Mijušković A, Oreščanin Dušić Z, Nikolić-Kokić A, Spasić M, Blagojević D. Ibogaine relaxes rat arteries: the role of endothelium. in FEBS3+ Meeting, Molecules of Life, Book of Abstracts. 2015;:194.
https://hdl.handle.net/21.15107/rcub_ibiss_4202 .

Tatalović, Nikola, Bajrica, Mina, Mijušković, Ana, Oreščanin Dušić, Zorana, Nikolić-Kokić, Aleksandra, Spasić, Mihajlo, Blagojević, Duško, "Ibogaine relaxes rat arteries: the role of endothelium" in FEBS3+ Meeting, Molecules of Life, Book of Abstracts (2015):194,
https://hdl.handle.net/21.15107/rcub_ibiss_4202 .

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 . .

TY  - JOUR
AU  - Milic, Sonja
AU  - Pristov, Jelena Bogdanovic
AU  - Mutavdzic, Dragosav
AU  - Savic, Aleksandar
AU  - Spasić, Mihajlo
AU  - Spasojevic, Ivan
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1971
AB  - Herein we compared antioxidative activities (AA) of 25 free L-amino
   acids (FAA) against Fenton system-mediated hydroxyl radical (HO center
   dot) production in aqueous solution, and examined the relation between
   AA and a set of physicochemical properties. The tank order according -to
   AA was: Tip > notleucine > Phe, Lett > Ile > His
   >3,4-dihydrOxyphenylalanine, Arg > Val > Lys, Tyr, Pro > hydtoxyproline
   > alpha-aminobutyric acid > Gln, Thr, Ser > Glu, Ala, Gly, Asn, Asp.
   Sulfur-containing FAA generated different secondary reactive products,
   which were discriminated by the means of electron paramagnetic resonance
   spin-trapping spectroscopy. AA showed a general positive correlation
   with hydrophobicity. However, when taken separately, uncharged FAA
   exhibited strong positive correlation of AA with hydrophobicity whereas
   charged FAA showed negative or no significant correlation depending on
   the scale applied. A general strong negative correlation was found
   between AA and polarity. Steric parameters and hydration numbers
   correlated positively with AA of rtoripolar side-chain FAA. In addition)
   a decrease of temperature which promotes hydrophobic hydration resulted
   in increased AA. This implies that HO-provoked oxidation of FAA is
   strongly affected by hydrophobic hydration. Our findings are important
   for the understanding of oxidation processes in natural and waste
   waters.
T2  - Environmental Science & Technology
T1  - The Relationship of Physicochemical Properties to the Antioxidative
 Activity of Free Amino Acids in Fenton System
IS  - 7
VL  - 49
DO  - 10.1021/es5053396
SP  - 4245
EP  - 4254
ER  - 

@article{
author = "Milic, Sonja and Pristov, Jelena Bogdanovic and Mutavdzic, Dragosav and Savic, Aleksandar and Spasić, Mihajlo and Spasojevic, Ivan",
year = "2015",
abstract = "Herein we compared antioxidative activities (AA) of 25 free L-amino
   acids (FAA) against Fenton system-mediated hydroxyl radical (HO center
   dot) production in aqueous solution, and examined the relation between
   AA and a set of physicochemical properties. The tank order according -to
   AA was: Tip > notleucine > Phe, Lett > Ile > His
   >3,4-dihydrOxyphenylalanine, Arg > Val > Lys, Tyr, Pro > hydtoxyproline
   > alpha-aminobutyric acid > Gln, Thr, Ser > Glu, Ala, Gly, Asn, Asp.
   Sulfur-containing FAA generated different secondary reactive products,
   which were discriminated by the means of electron paramagnetic resonance
   spin-trapping spectroscopy. AA showed a general positive correlation
   with hydrophobicity. However, when taken separately, uncharged FAA
   exhibited strong positive correlation of AA with hydrophobicity whereas
   charged FAA showed negative or no significant correlation depending on
   the scale applied. A general strong negative correlation was found
   between AA and polarity. Steric parameters and hydration numbers
   correlated positively with AA of rtoripolar side-chain FAA. In addition)
   a decrease of temperature which promotes hydrophobic hydration resulted
   in increased AA. This implies that HO-provoked oxidation of FAA is
   strongly affected by hydrophobic hydration. Our findings are important
   for the understanding of oxidation processes in natural and waste
   waters.",
journal = "Environmental Science & Technology",
title = "The Relationship of Physicochemical Properties to the Antioxidative
 Activity of Free Amino Acids in Fenton System",
number = "7",
volume = "49",
doi = "10.1021/es5053396",
pages = "4245-4254"
}

Milic, S., Pristov, J. B., Mutavdzic, D., Savic, A., Spasić, M.,& Spasojevic, I.. (2015). The Relationship of Physicochemical Properties to the Antioxidative
 Activity of Free Amino Acids in Fenton System. in Environmental Science & Technology, 49(7), 4245-4254.
https://doi.org/10.1021/es5053396

Milic S, Pristov JB, Mutavdzic D, Savic A, Spasić M, Spasojevic I. The Relationship of Physicochemical Properties to the Antioxidative
 Activity of Free Amino Acids in Fenton System. in Environmental Science & Technology. 2015;49(7):4245-4254.
doi:10.1021/es5053396 .

Milic, Sonja, Pristov, Jelena Bogdanovic, Mutavdzic, Dragosav, Savic, Aleksandar, Spasić, Mihajlo, Spasojevic, Ivan, "The Relationship of Physicochemical Properties to the Antioxidative
 Activity of Free Amino Acids in Fenton System" in Environmental Science & Technology, 49, no. 7 (2015):4245-4254,
https://doi.org/10.1021/es5053396 . .

TY  - JOUR
AU  - Bolic, Bojana
AU  - Mijuskovic, Ana
AU  - Popovic-Bijelic, Ana
AU  - Nikolić-Kokić, Aleksandra
AU  - Spasic, Snezana
AU  - Blagojević, Duško
AU  - Spasić, Mihajlo
AU  - Spasojevic, Ivan
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2329
AB  - Interactions of hydrogen sulfide (HS-/H2S), a reducing signaling
   species, with superoxide dimutases (SOD) are poorly understood. We
   applied low-T EPR spectroscopy to examine the effects of HS-/H2S and
   superoxide radical anion (O-2(-)) on metallocenters of FeSOD, MnSOD, and
   CuZnSOD. HS-/H2S did not affect FeSOD, whereas active centers of MnSOD
   and CuZnSOD were open to this agent. Cu2+ was reduced to Cu1+, while
   manganese appears to be released from MnSOD active center. Untreated and
   O-2(-) treated FeSOD and MnSOD predominantly show 5 d-electron systems,
   i.e. Fe3+ and Mn2+. Our study provides new details on the mechanisms of
   (patho)physiological effects of HS-/H2S. (C) 2015 Elsevier Inc. All
   rights reserved.
T2  - Nitric Oxide-Biology and Chemistry
T1  - Reactions of superoxide dismutases with HS-/H2S and superoxide radical
 anion: An in vitro EPR study
VL  - 51
DO  - 10.1016/j.niox.2015.09.008
SP  - 19
EP  - 23
ER  - 

@article{
author = "Bolic, Bojana and Mijuskovic, Ana and Popovic-Bijelic, Ana and Nikolić-Kokić, Aleksandra and Spasic, Snezana and Blagojević, Duško and Spasić, Mihajlo and Spasojevic, Ivan",
year = "2015",
abstract = "Interactions of hydrogen sulfide (HS-/H2S), a reducing signaling
   species, with superoxide dimutases (SOD) are poorly understood. We
   applied low-T EPR spectroscopy to examine the effects of HS-/H2S and
   superoxide radical anion (O-2(-)) on metallocenters of FeSOD, MnSOD, and
   CuZnSOD. HS-/H2S did not affect FeSOD, whereas active centers of MnSOD
   and CuZnSOD were open to this agent. Cu2+ was reduced to Cu1+, while
   manganese appears to be released from MnSOD active center. Untreated and
   O-2(-) treated FeSOD and MnSOD predominantly show 5 d-electron systems,
   i.e. Fe3+ and Mn2+. Our study provides new details on the mechanisms of
   (patho)physiological effects of HS-/H2S. (C) 2015 Elsevier Inc. All
   rights reserved.",
journal = "Nitric Oxide-Biology and Chemistry",
title = "Reactions of superoxide dismutases with HS-/H2S and superoxide radical
 anion: An in vitro EPR study",
volume = "51",
doi = "10.1016/j.niox.2015.09.008",
pages = "19-23"
}

Bolic, B., Mijuskovic, A., Popovic-Bijelic, A., Nikolić-Kokić, A., Spasic, S., Blagojević, D., Spasić, M.,& Spasojevic, I.. (2015). Reactions of superoxide dismutases with HS-/H2S and superoxide radical
 anion: An in vitro EPR study. in Nitric Oxide-Biology and Chemistry, 51, 19-23.
https://doi.org/10.1016/j.niox.2015.09.008

Bolic B, Mijuskovic A, Popovic-Bijelic A, Nikolić-Kokić A, Spasic S, Blagojević D, Spasić M, Spasojevic I. Reactions of superoxide dismutases with HS-/H2S and superoxide radical
 anion: An in vitro EPR study. in Nitric Oxide-Biology and Chemistry. 2015;51:19-23.
doi:10.1016/j.niox.2015.09.008 .

Bolic, Bojana, Mijuskovic, Ana, Popovic-Bijelic, Ana, Nikolić-Kokić, Aleksandra, Spasic, Snezana, Blagojević, Duško, Spasić, Mihajlo, Spasojevic, Ivan, "Reactions of superoxide dismutases with HS-/H2S and superoxide radical
 anion: An in vitro EPR study" in Nitric Oxide-Biology and Chemistry, 51 (2015):19-23,
https://doi.org/10.1016/j.niox.2015.09.008 . .

TY  - CONF
AU  - Mijuskovic, Ana
AU  - Oreščanin Dušić, Zorana
AU  - Nikolić-Kokić, Aleksandra
AU  - Slavic, Marija
AU  - Spasić, Mihajlo
AU  - Spasojevic, Ivan
AU  - Blagojević, Duško
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2211
C3  - Nitric Oxide-Biology and Chemistry
T1  - Sodium sulphide relaxation of rat uterus is related to calcium signaling
IS  - 1
VL  - 39
DO  - 10.1016/j.niox.2014.03.119
SP  - S36
EP  - S37
ER  - 

@conference{
author = "Mijuskovic, Ana and Oreščanin Dušić, Zorana and Nikolić-Kokić, Aleksandra and Slavic, Marija and Spasić, Mihajlo and Spasojevic, Ivan and Blagojević, Duško",
year = "2014",
journal = "Nitric Oxide-Biology and Chemistry",
title = "Sodium sulphide relaxation of rat uterus is related to calcium signaling",
number = "1",
volume = "39",
doi = "10.1016/j.niox.2014.03.119",
pages = "S36-S37"
}

Mijuskovic, A., Oreščanin Dušić, Z., Nikolić-Kokić, A., Slavic, M., Spasić, M., Spasojevic, I.,& Blagojević, D.. (2014). Sodium sulphide relaxation of rat uterus is related to calcium signaling. in Nitric Oxide-Biology and Chemistry, 39(1), S36-S37.
https://doi.org/10.1016/j.niox.2014.03.119

Mijuskovic A, Oreščanin Dušić Z, Nikolić-Kokić A, Slavic M, Spasić M, Spasojevic I, Blagojević D. Sodium sulphide relaxation of rat uterus is related to calcium signaling. in Nitric Oxide-Biology and Chemistry. 2014;39(1):S36-S37.
doi:10.1016/j.niox.2014.03.119 .

Mijuskovic, Ana, Oreščanin Dušić, Zorana, Nikolić-Kokić, Aleksandra, Slavic, Marija, Spasić, Mihajlo, Spasojevic, Ivan, Blagojević, Duško, "Sodium sulphide relaxation of rat uterus is related to calcium signaling" in Nitric Oxide-Biology and Chemistry, 39, no. 1 (2014):S36-S37,
https://doi.org/10.1016/j.niox.2014.03.119 . .

TY  - JOUR
AU  - Marković, Snežana D.
AU  - Đorđević, Nataša Z.
AU  - Ćurčić, Milena G.
AU  - Štajn, Andraš Š.
AU  - Spasić, Mihajlo
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2151
AB  - The effects of nitroglycerin (glyceryl trinitrate - GTN) are mediated by
   liberated nitric oxide (NO) and formed reactive nitrogen species, which
   induces oxidative stress during biotransformation in red blood cells
   (RBCs). The aim of this study was to evaluate effects of GTN on
   antioxidative defense system (AOS) in rat erythrocytes (without) and
   reticulocytes (with functional mitochondria). Rat erythrocyte and
   reticulocyte-rich RBC suspensions were aerobically incubated (2 h, 37
   degrees C) without (control) or in the presence of different
   concentrations of GTN (0.1-1.5 mM). After incubation, concentrations of
   non-enzymatic components of AOS, activities of antioxidative enzymes and
   oxidative pentose phosphate (OPP) pathway activity were followed in RBC
   suspensions. In rat reticulocytes, GTN decreased the activity of
   mitochondrial MnSOD and increased the activity of CuZnSOD. In rat RBCs,
   GTN induced increase of Vit E concentration (at high doses), but
   decreased glutathione content and activities of all
   glutathione-dependent antioxidative enzymes; the OPP pathway activity
   significantly increased. GTN biotransformation and induction of
   oxidative stress were followed by general disbalance of antioxidative
   capacities in both kinds of RBCs. We suggest that oxidative stress,
   MnSOD inhibition and depletion of glutathione pool in response to GTN
   treatment lead to decreased bioavailability of NO after GTN
   biotransformation in rat reticulocytes.
T2  - General Physiology and Biophysics
T1  - Biotransformation and nitroglycerin-induced effects on antioxidative
 defense system in rat erythrocytes and reticulocytes
IS  - 4
VL  - 33
DO  - 10.4149/gpb_2014018
SP  - 393
EP  - 401
ER  - 

@article{
author = "Marković, Snežana D. and Đorđević, Nataša Z. and Ćurčić, Milena G. and Štajn, Andraš Š. and Spasić, Mihajlo",
year = "2014",
abstract = "The effects of nitroglycerin (glyceryl trinitrate - GTN) are mediated by
   liberated nitric oxide (NO) and formed reactive nitrogen species, which
   induces oxidative stress during biotransformation in red blood cells
   (RBCs). The aim of this study was to evaluate effects of GTN on
   antioxidative defense system (AOS) in rat erythrocytes (without) and
   reticulocytes (with functional mitochondria). Rat erythrocyte and
   reticulocyte-rich RBC suspensions were aerobically incubated (2 h, 37
   degrees C) without (control) or in the presence of different
   concentrations of GTN (0.1-1.5 mM). After incubation, concentrations of
   non-enzymatic components of AOS, activities of antioxidative enzymes and
   oxidative pentose phosphate (OPP) pathway activity were followed in RBC
   suspensions. In rat reticulocytes, GTN decreased the activity of
   mitochondrial MnSOD and increased the activity of CuZnSOD. In rat RBCs,
   GTN induced increase of Vit E concentration (at high doses), but
   decreased glutathione content and activities of all
   glutathione-dependent antioxidative enzymes; the OPP pathway activity
   significantly increased. GTN biotransformation and induction of
   oxidative stress were followed by general disbalance of antioxidative
   capacities in both kinds of RBCs. We suggest that oxidative stress,
   MnSOD inhibition and depletion of glutathione pool in response to GTN
   treatment lead to decreased bioavailability of NO after GTN
   biotransformation in rat reticulocytes.",
journal = "General Physiology and Biophysics",
title = "Biotransformation and nitroglycerin-induced effects on antioxidative
 defense system in rat erythrocytes and reticulocytes",
number = "4",
volume = "33",
doi = "10.4149/gpb_2014018",
pages = "393-401"
}

Marković, S. D., Đorđević, N. Z., Ćurčić, M. G., Štajn, A. Š.,& Spasić, M.. (2014). Biotransformation and nitroglycerin-induced effects on antioxidative
 defense system in rat erythrocytes and reticulocytes. in General Physiology and Biophysics, 33(4), 393-401.
https://doi.org/10.4149/gpb_2014018

Marković SD, Đorđević NZ, Ćurčić MG, Štajn AŠ, Spasić M. Biotransformation and nitroglycerin-induced effects on antioxidative
 defense system in rat erythrocytes and reticulocytes. in General Physiology and Biophysics. 2014;33(4):393-401.
doi:10.4149/gpb_2014018 .

Marković, Snežana D., Đorđević, Nataša Z., Ćurčić, Milena G., Štajn, Andraš Š., Spasić, Mihajlo, "Biotransformation and nitroglycerin-induced effects on antioxidative
 defense system in rat erythrocytes and reticulocytes" in General Physiology and Biophysics, 33, no. 4 (2014):393-401,
https://doi.org/10.4149/gpb_2014018 . .

TY  - JOUR
AU  - Mijuskovic, Ana
AU  - Oreščanin Dušić, Zorana
AU  - Nikolić-Kokić, Aleksandra
AU  - Slavic, Marija
AU  - Spasić, Mihajlo
AU  - Spasojevic, Ivan
AU  - Blagojević, Duško
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2206
AB  - Background: Our aim was to investigate the effect of methanethiol
   (CH3SH) on contractility of rat uterus and activities of redox-active
   enzymes, and to compare them with the effect of sodium sulphide (Na2S),
   a hydrogen sulphide (H2S/HS-) donor.
   Methods: Uteri were isolated from virgin Wistar rats, divided into six
   groups, controls (untreated uteri allowed to contract spontaneously and
   in the presence of Ca2+(6 mM)), CH3SH treated (spontaneously active and
   Ca2+ induced) and Na2S treated (spontaneously active and Ca2+ induced).
   Underlying antioxidative enzyme activities (superoxide dismutase - SOD,
   glutathione peroxidase - GSHPx, glutathione reductase - GR) in CH3SH- or
   Na2S-treated uteri were compared to controls.
   Results: Our experiments showed that CH3SH and Na2S provoked reversible
   relaxation of both spontaneous and Ca2+ induced uterine contractions.
   The dose-response curves differed in shape, and CH3SH curve was shifted
   to higher concentration compared to H2S/HS-. The effects of Na2S fitted
   sigmoid curve, whereas those of CH3SH fitted linearly. CH3SH provoked
   increased SOD activity and decreased GR activity. However, Na2S
   (H2S/HS-) provoked an increase in SOD activity exclusively in Ca2+
   stimulated uteri, while the activity of GSHPx was increased in both
   types of active uteri.
   Conclusion: Our results imply that CH3SH may have a constructive role in
   the control of muscle function and metabolism. Observed differences
   between CH3SH and H2S/HS- could be attributed to a larger moiety that is
   present in CH3SH compared to H2S, but they are more likely to be a
   consequence of the specific actions of HS-, in relation to its negative
   charge. (C) 2014 Institute of Pharmacology, Polish Academy of Sciences.
   Published by Elsevier Urban \& Partner Sp. Z o.o.. All rights reserved.
T2  - Pharmacological Reports
T1  - Comparison of the effects of methanethiol and sodium sulphide on uterine
 contractile activity
IS  - 3
VL  - 66
DO  - 10.1016/j.pharep.2013.12.012
SP  - 373
EP  - 379
ER  - 

@article{
author = "Mijuskovic, Ana and Oreščanin Dušić, Zorana and Nikolić-Kokić, Aleksandra and Slavic, Marija and Spasić, Mihajlo and Spasojevic, Ivan and Blagojević, Duško",
year = "2014",
abstract = "Background: Our aim was to investigate the effect of methanethiol
   (CH3SH) on contractility of rat uterus and activities of redox-active
   enzymes, and to compare them with the effect of sodium sulphide (Na2S),
   a hydrogen sulphide (H2S/HS-) donor.
   Methods: Uteri were isolated from virgin Wistar rats, divided into six
   groups, controls (untreated uteri allowed to contract spontaneously and
   in the presence of Ca2+(6 mM)), CH3SH treated (spontaneously active and
   Ca2+ induced) and Na2S treated (spontaneously active and Ca2+ induced).
   Underlying antioxidative enzyme activities (superoxide dismutase - SOD,
   glutathione peroxidase - GSHPx, glutathione reductase - GR) in CH3SH- or
   Na2S-treated uteri were compared to controls.
   Results: Our experiments showed that CH3SH and Na2S provoked reversible
   relaxation of both spontaneous and Ca2+ induced uterine contractions.
   The dose-response curves differed in shape, and CH3SH curve was shifted
   to higher concentration compared to H2S/HS-. The effects of Na2S fitted
   sigmoid curve, whereas those of CH3SH fitted linearly. CH3SH provoked
   increased SOD activity and decreased GR activity. However, Na2S
   (H2S/HS-) provoked an increase in SOD activity exclusively in Ca2+
   stimulated uteri, while the activity of GSHPx was increased in both
   types of active uteri.
   Conclusion: Our results imply that CH3SH may have a constructive role in
   the control of muscle function and metabolism. Observed differences
   between CH3SH and H2S/HS- could be attributed to a larger moiety that is
   present in CH3SH compared to H2S, but they are more likely to be a
   consequence of the specific actions of HS-, in relation to its negative
   charge. (C) 2014 Institute of Pharmacology, Polish Academy of Sciences.
   Published by Elsevier Urban \& Partner Sp. Z o.o.. All rights reserved.",
journal = "Pharmacological Reports",
title = "Comparison of the effects of methanethiol and sodium sulphide on uterine
 contractile activity",
number = "3",
volume = "66",
doi = "10.1016/j.pharep.2013.12.012",
pages = "373-379"
}

Mijuskovic, A., Oreščanin Dušić, Z., Nikolić-Kokić, A., Slavic, M., Spasić, M., Spasojevic, I.,& Blagojević, D.. (2014). Comparison of the effects of methanethiol and sodium sulphide on uterine
 contractile activity. in Pharmacological Reports, 66(3), 373-379.
https://doi.org/10.1016/j.pharep.2013.12.012

Mijuskovic A, Oreščanin Dušić Z, Nikolić-Kokić A, Slavic M, Spasić M, Spasojevic I, Blagojević D. Comparison of the effects of methanethiol and sodium sulphide on uterine
 contractile activity. in Pharmacological Reports. 2014;66(3):373-379.
doi:10.1016/j.pharep.2013.12.012 .

Mijuskovic, Ana, Oreščanin Dušić, Zorana, Nikolić-Kokić, Aleksandra, Slavic, Marija, Spasić, Mihajlo, Spasojevic, Ivan, Blagojević, Duško, "Comparison of the effects of methanethiol and sodium sulphide on uterine
 contractile activity" in Pharmacological Reports, 66, no. 3 (2014):373-379,
https://doi.org/10.1016/j.pharep.2013.12.012 . .