TY  - JOUR
AU  - Todorović, Zoran B.
AU  - Đurašević, Siniša
AU  - Stojković, Maja
AU  - Grigorov, Ilijana
AU  - Pavlović, Slađan Z.
AU  - Jasnić, Nebojša
AU  - Tosti, Tomislav
AU  - Macut Bjekić, Jelica
AU  - Thiemermann, Christoph
AU  - Popović-Đorđević, Jelena
PY  - 2021
UR  - https://www.mdpi.com/1422-0067/22/6/2798
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/4512
AB  - Lipids play an essential role in both tissue protection and damage. Tissue ischemia creates anaerobic conditions in which enzyme inactivation occurs, and reperfusion can initiate oxidative stress that leads to harmful changes in membrane lipids, the formation of aldehydes, and chain damage until cell death. The critical event in such a series of harmful events in the cell is the unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of ischemia/reperfusion (I/R) disorders and reveals new targets for drug action. The profile of changes in the composition of fatty acids in the cell, as well as the time course of these changes, indicate both the mechanism of damage and new therapeutic possibilities. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes.
PB  - MDPI
T2  - International Journal of Molecular Sciences
T2  - International Journal of Molecular Sciences
T1  - Lipidomics provides new insight into pathogenesis and therapeutic targets of the ischemia—reperfusion injury
VL  - 22
IS  - 6
SP  - 2798
DO  - 10.3390/ijms22062798
ER  - 

@article{
author = "Todorović, Zoran B. and Đurašević, Siniša and Stojković, Maja and Grigorov, Ilijana and Pavlović, Slađan Z. and Jasnić, Nebojša and Tosti, Tomislav and Macut Bjekić, Jelica and Thiemermann, Christoph and Popović-Đorđević, Jelena",
year = "2021",
abstract = "Lipids play an essential role in both tissue protection and damage. Tissue ischemia creates anaerobic conditions in which enzyme inactivation occurs, and reperfusion can initiate oxidative stress that leads to harmful changes in membrane lipids, the formation of aldehydes, and chain damage until cell death. The critical event in such a series of harmful events in the cell is the unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of ischemia/reperfusion (I/R) disorders and reveals new targets for drug action. The profile of changes in the composition of fatty acids in the cell, as well as the time course of these changes, indicate both the mechanism of damage and new therapeutic possibilities. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes.",
publisher = "MDPI",
journal = "International Journal of Molecular Sciences, International Journal of Molecular Sciences",
title = "Lipidomics provides new insight into pathogenesis and therapeutic targets of the ischemia—reperfusion injury",
volume = "22",
number = "6",
pages = "2798",
doi = "10.3390/ijms22062798"
}

Todorović, Z. B., Đurašević, S., Stojković, M., Grigorov, I., Pavlović, S. Z., Jasnić, N., Tosti, T., Macut Bjekić, J., Thiemermann, C.,& Popović-Đorđević, J.. (2021). Lipidomics provides new insight into pathogenesis and therapeutic targets of the ischemia—reperfusion injury. in International Journal of Molecular Sciences
MDPI., 22(6), 2798.
https://doi.org/10.3390/ijms22062798

Todorović ZB, Đurašević S, Stojković M, Grigorov I, Pavlović SZ, Jasnić N, Tosti T, Macut Bjekić J, Thiemermann C, Popović-Đorđević J. Lipidomics provides new insight into pathogenesis and therapeutic targets of the ischemia—reperfusion injury. in International Journal of Molecular Sciences. 2021;22(6):2798.
doi:10.3390/ijms22062798 .

Todorović, Zoran B., Đurašević, Siniša, Stojković, Maja, Grigorov, Ilijana, Pavlović, Slađan Z., Jasnić, Nebojša, Tosti, Tomislav, Macut Bjekić, Jelica, Thiemermann, Christoph, Popović-Đorđević, Jelena, "Lipidomics provides new insight into pathogenesis and therapeutic targets of the ischemia—reperfusion injury" in International Journal of Molecular Sciences, 22, no. 6 (2021):2798,
https://doi.org/10.3390/ijms22062798 . .

TY  - JOUR
AU  - Đurašević, Siniša
AU  - Ružičić, Aleksandra
AU  - Lakić, Iva
AU  - Tosti, Tomislav
AU  - Đurović, Saša
AU  - Glumac, Sofija
AU  - Pavlović, Slađan Z.
AU  - Borković-Mitić, Slavica S.
AU  - Grigorov, Ilijana
AU  - Stanković, Sanja
AU  - Jasnić, Nebojša
AU  - Popović-Đorđević, Jelena
AU  - Todorović, Zoran B.
PY  - 2021
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/4671
AB  - Sepsis is a life-threatening condition caused by the dysregulated and overwhelming response to infection, accompanied by an exaggerated pro-inflammatory state and lipid metabolism disturbance leading to sequential organ failure. Meldonium is an anti-ischemic and anti-inflammatory agent which negatively interferes with lipid metabolism by shifting energy production from fatty acid oxidation to glycolysis, as a less oxygen-demanding pathway. Thus, we investigated the effects of a four-week meldonium pre-treatment on faecal-induced sepsis in Sprague-Dawley male rats. Surprisingly, under septic conditions, meldonium increased animal mortality rate compared with the meldonium non-treated group. However, analysis of the tissue oxidative status did not provide support for the detrimental effects of meldonium, nor did the analysis of the tissue inflammatory status showing anti-inflammatory, anti-apoptotic, and anti-necrotic effects of meldonium. After performing tissue lipidomic analysis, we concluded that the potential cause of the meldonium harmful effect is to be found in the overall decreased lipid metabolism. The present study underlines the importance of uninterrupted energy production in sepsis, closely drawing attention to the possible harmful effects of lipid-mobilization impairment caused by certain therapeutics. This could lead to the much-needed revision of the existing guidelines in the clinical treatment of sepsis while paving the way for discovering new therapeutic approaches.
PB  - MDPI
T2  - International Journal of Molecular Sciences
T1  - The Effects of a Meldonium Pre-Treatment on the Course of the Faecal-Induced Sepsis in Rats
VL  - 22
IS  - 18
SP  - 9698
DO  - 10.3390/ijms22189698
ER  - 

@article{
author = "Đurašević, Siniša and Ružičić, Aleksandra and Lakić, Iva and Tosti, Tomislav and Đurović, Saša and Glumac, Sofija and Pavlović, Slađan Z. and Borković-Mitić, Slavica S. and Grigorov, Ilijana and Stanković, Sanja and Jasnić, Nebojša and Popović-Đorđević, Jelena and Todorović, Zoran B.",
year = "2021",
abstract = "Sepsis is a life-threatening condition caused by the dysregulated and overwhelming response to infection, accompanied by an exaggerated pro-inflammatory state and lipid metabolism disturbance leading to sequential organ failure. Meldonium is an anti-ischemic and anti-inflammatory agent which negatively interferes with lipid metabolism by shifting energy production from fatty acid oxidation to glycolysis, as a less oxygen-demanding pathway. Thus, we investigated the effects of a four-week meldonium pre-treatment on faecal-induced sepsis in Sprague-Dawley male rats. Surprisingly, under septic conditions, meldonium increased animal mortality rate compared with the meldonium non-treated group. However, analysis of the tissue oxidative status did not provide support for the detrimental effects of meldonium, nor did the analysis of the tissue inflammatory status showing anti-inflammatory, anti-apoptotic, and anti-necrotic effects of meldonium. After performing tissue lipidomic analysis, we concluded that the potential cause of the meldonium harmful effect is to be found in the overall decreased lipid metabolism. The present study underlines the importance of uninterrupted energy production in sepsis, closely drawing attention to the possible harmful effects of lipid-mobilization impairment caused by certain therapeutics. This could lead to the much-needed revision of the existing guidelines in the clinical treatment of sepsis while paving the way for discovering new therapeutic approaches.",
publisher = "MDPI",
journal = "International Journal of Molecular Sciences",
title = "The Effects of a Meldonium Pre-Treatment on the Course of the Faecal-Induced Sepsis in Rats",
volume = "22",
number = "18",
pages = "9698",
doi = "10.3390/ijms22189698"
}

Đurašević, S., Ružičić, A., Lakić, I., Tosti, T., Đurović, S., Glumac, S., Pavlović, S. Z., Borković-Mitić, S. S., Grigorov, I., Stanković, S., Jasnić, N., Popović-Đorđević, J.,& Todorović, Z. B.. (2021). The Effects of a Meldonium Pre-Treatment on the Course of the Faecal-Induced Sepsis in Rats. in International Journal of Molecular Sciences
MDPI., 22(18), 9698.
https://doi.org/10.3390/ijms22189698

Đurašević S, Ružičić A, Lakić I, Tosti T, Đurović S, Glumac S, Pavlović SZ, Borković-Mitić SS, Grigorov I, Stanković S, Jasnić N, Popović-Đorđević J, Todorović ZB. The Effects of a Meldonium Pre-Treatment on the Course of the Faecal-Induced Sepsis in Rats. in International Journal of Molecular Sciences. 2021;22(18):9698.
doi:10.3390/ijms22189698 .

Đurašević, Siniša, Ružičić, Aleksandra, Lakić, Iva, Tosti, Tomislav, Đurović, Saša, Glumac, Sofija, Pavlović, Slađan Z., Borković-Mitić, Slavica S., Grigorov, Ilijana, Stanković, Sanja, Jasnić, Nebojša, Popović-Đorđević, Jelena, Todorović, Zoran B., "The Effects of a Meldonium Pre-Treatment on the Course of the Faecal-Induced Sepsis in Rats" in International Journal of Molecular Sciences, 22, no. 18 (2021):9698,
https://doi.org/10.3390/ijms22189698 . .

TY  - JOUR
AU  - Đurašević, Siniša
AU  - Stojković, Maja
AU  - Bogdanović, Ljiljana
AU  - Pavlović, Slađan Z.
AU  - Borković-Mitić, Slavica S.
AU  - Grigorov, Ilijana
AU  - Bogojević, Desanka
AU  - Jasnić, Nebojša
AU  - Tosti, Tomislav
AU  - Đurović, Saša
AU  - Popović-Đorđević, Jelena
AU  - Todorović, Zoran B.
PY  - 2019
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3767
AB  - Acute renal ischemia/reperfusion (I/R) injury is a clinical condition that is challenging to treat. Meldonium is an anti-ischemic agent that shifts energy production from fatty acid oxidation to less oxygen-consuming glycolysis. Thus, in this study we investigated the effects of a four-week meldonium pre-treatment (300 mg/kg b.m./day) on acute renal I/R in male rats (Wistar strain). Our results showed that meldonium decreased animal body mass gain, food and water intake, and carnitine, glucose, and lactic acid kidney content. In kidneys of animals subjected to I/R, meldonium increased phosphorylation of mitogen-activated protein kinase p38 and protein kinase B, and increased the expression of nuclear factor erythroid 2-related factor 2 and haeme oxygenase 1, causing manganese superoxide dismutase expression and activity to increase, as well as lipid peroxidation, cooper-zinc superoxide dismutase, glutathione peroxidase, and glutathione reductase activities to decrease. By decreasing the kidney Bax/Bcl2 expression ratio and kidney and serum high mobility group box 1 protein content, meldonium reduced apoptotic and necrotic events in I/R, as confirmed by kidney histology. Meldonium increased adrenal noradrenaline content and serum, adrenal, hepatic, and renal ascorbic/dehydroascorbic acid ratio, which caused complex changes in renal lipidomics. Taken together, our results have confirmed that meldonium pretreatment protects against I/R-induced oxidative stress and apoptosis/necrosis.
PB  - MDPI
T2  - International Journal of Molecular Sciences
T1  - The effects of meldonium on the renal acute ischemia/reperfusion injury in rats
VL  - 20
IS  - 22
DO  - 10.3390/ijms20225747
ER  - 

@article{
author = "Đurašević, Siniša and Stojković, Maja and Bogdanović, Ljiljana and Pavlović, Slađan Z. and Borković-Mitić, Slavica S. and Grigorov, Ilijana and Bogojević, Desanka and Jasnić, Nebojša and Tosti, Tomislav and Đurović, Saša and Popović-Đorđević, Jelena and Todorović, Zoran B.",
year = "2019",
abstract = "Acute renal ischemia/reperfusion (I/R) injury is a clinical condition that is challenging to treat. Meldonium is an anti-ischemic agent that shifts energy production from fatty acid oxidation to less oxygen-consuming glycolysis. Thus, in this study we investigated the effects of a four-week meldonium pre-treatment (300 mg/kg b.m./day) on acute renal I/R in male rats (Wistar strain). Our results showed that meldonium decreased animal body mass gain, food and water intake, and carnitine, glucose, and lactic acid kidney content. In kidneys of animals subjected to I/R, meldonium increased phosphorylation of mitogen-activated protein kinase p38 and protein kinase B, and increased the expression of nuclear factor erythroid 2-related factor 2 and haeme oxygenase 1, causing manganese superoxide dismutase expression and activity to increase, as well as lipid peroxidation, cooper-zinc superoxide dismutase, glutathione peroxidase, and glutathione reductase activities to decrease. By decreasing the kidney Bax/Bcl2 expression ratio and kidney and serum high mobility group box 1 protein content, meldonium reduced apoptotic and necrotic events in I/R, as confirmed by kidney histology. Meldonium increased adrenal noradrenaline content and serum, adrenal, hepatic, and renal ascorbic/dehydroascorbic acid ratio, which caused complex changes in renal lipidomics. Taken together, our results have confirmed that meldonium pretreatment protects against I/R-induced oxidative stress and apoptosis/necrosis.",
publisher = "MDPI",
journal = "International Journal of Molecular Sciences",
title = "The effects of meldonium on the renal acute ischemia/reperfusion injury in rats",
volume = "20",
number = "22",
doi = "10.3390/ijms20225747"
}

Đurašević, S., Stojković, M., Bogdanović, L., Pavlović, S. Z., Borković-Mitić, S. S., Grigorov, I., Bogojević, D., Jasnić, N., Tosti, T., Đurović, S., Popović-Đorđević, J.,& Todorović, Z. B.. (2019). The effects of meldonium on the renal acute ischemia/reperfusion injury in rats. in International Journal of Molecular Sciences
MDPI., 20(22).
https://doi.org/10.3390/ijms20225747

Đurašević S, Stojković M, Bogdanović L, Pavlović SZ, Borković-Mitić SS, Grigorov I, Bogojević D, Jasnić N, Tosti T, Đurović S, Popović-Đorđević J, Todorović ZB. The effects of meldonium on the renal acute ischemia/reperfusion injury in rats. in International Journal of Molecular Sciences. 2019;20(22).
doi:10.3390/ijms20225747 .

Đurašević, Siniša, Stojković, Maja, Bogdanović, Ljiljana, Pavlović, Slađan Z., Borković-Mitić, Slavica S., Grigorov, Ilijana, Bogojević, Desanka, Jasnić, Nebojša, Tosti, Tomislav, Đurović, Saša, Popović-Đorđević, Jelena, Todorović, Zoran B., "The effects of meldonium on the renal acute ischemia/reperfusion injury in rats" in International Journal of Molecular Sciences, 20, no. 22 (2019),
https://doi.org/10.3390/ijms20225747 . .

TY  - JOUR
AU  - Ninkov, Marina
AU  - Popov-Aleksandrov, Aleksandra
AU  - Demenesku, Jelena
AU  - Mirkov, Ivana
AU  - Mileusnić, Dina
AU  - Petrović, Anja
AU  - Grigorov, Ilijana
AU  - Zolotarevski, Lidija
AU  - Tolinački, Maja
AU  - Kataranovski, Dragan
AU  - Brčeski, Ilija
AU  - Kataranovski, Milena
PY  - 2015
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1730
AB  - Gastrointestinal tract is one of the main targets of cadmium (Cd), an important food and drinking water contaminant. In the present study, the effect of subchronic (30 days) oral (in water) intake of 5ppm and 50ppm of cadmium on immune responses in the gut was examined in rats. Cadmium consumption resulted in reduction of bacteria corresponding to Lactobacillus strain, tissue damage and intestinal inflammation [increases in high mobility group box 1 (HMGB1 molecules), superoxide dismutase (SOD) and catalase (CAT) activity and proinflammatory cytokine (TNF, IL-1 beta, IFN-gamma, IL-17) content]. Draining (mesenteric) lymph node (MLN) stress response was observed [elevation of MLN glutathione (GSH) and metallothionein (MT) mRNA levels] and stimulation of both adaptive [cellularity, proliferation, proinflammatory (IFN-gamma and IL-17) MLN cell cytokine responses] as well as innate immune activity (increases in numbers of NK and CD68(+) cells, oxidative activities, IL-1 beta). In contrast to proinflammatory milieu in MLN, decreased or unchanged antiinflammatory IL-10 response was observed. Stimulation of immune activities of MLN cells have, most probably, resulted from sensing of cadmium-induced tissue injury, but also from bacterial antigens that breached compromised intestinal barrier. These effects of cadmium should be taken into account when assessing dietary cadmium as health risk factor. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
PB  - Elsevier Ireland Ltd, Clare
T2  - Toxicology Letters
T1  - Toxicity of oral cadmium intake: Impact on gut immunity
VL  - 237
IS  - 2
SP  - 89
EP  - 99
DO  - 10.1016/j.toxlet.2015.06.002
ER  - 

@article{
author = "Ninkov, Marina and Popov-Aleksandrov, Aleksandra and Demenesku, Jelena and Mirkov, Ivana and Mileusnić, Dina and Petrović, Anja and Grigorov, Ilijana and Zolotarevski, Lidija and Tolinački, Maja and Kataranovski, Dragan and Brčeski, Ilija and Kataranovski, Milena",
year = "2015",
abstract = "Gastrointestinal tract is one of the main targets of cadmium (Cd), an important food and drinking water contaminant. In the present study, the effect of subchronic (30 days) oral (in water) intake of 5ppm and 50ppm of cadmium on immune responses in the gut was examined in rats. Cadmium consumption resulted in reduction of bacteria corresponding to Lactobacillus strain, tissue damage and intestinal inflammation [increases in high mobility group box 1 (HMGB1 molecules), superoxide dismutase (SOD) and catalase (CAT) activity and proinflammatory cytokine (TNF, IL-1 beta, IFN-gamma, IL-17) content]. Draining (mesenteric) lymph node (MLN) stress response was observed [elevation of MLN glutathione (GSH) and metallothionein (MT) mRNA levels] and stimulation of both adaptive [cellularity, proliferation, proinflammatory (IFN-gamma and IL-17) MLN cell cytokine responses] as well as innate immune activity (increases in numbers of NK and CD68(+) cells, oxidative activities, IL-1 beta). In contrast to proinflammatory milieu in MLN, decreased or unchanged antiinflammatory IL-10 response was observed. Stimulation of immune activities of MLN cells have, most probably, resulted from sensing of cadmium-induced tissue injury, but also from bacterial antigens that breached compromised intestinal barrier. These effects of cadmium should be taken into account when assessing dietary cadmium as health risk factor. (C) 2015 Elsevier Ireland Ltd. All rights reserved.",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Toxicology Letters",
title = "Toxicity of oral cadmium intake: Impact on gut immunity",
volume = "237",
number = "2",
pages = "89-99",
doi = "10.1016/j.toxlet.2015.06.002"
}

Ninkov, M., Popov-Aleksandrov, A., Demenesku, J., Mirkov, I., Mileusnić, D., Petrović, A., Grigorov, I., Zolotarevski, L., Tolinački, M., Kataranovski, D., Brčeski, I.,& Kataranovski, M.. (2015). Toxicity of oral cadmium intake: Impact on gut immunity. in Toxicology Letters
Elsevier Ireland Ltd, Clare., 237(2), 89-99.
https://doi.org/10.1016/j.toxlet.2015.06.002

Ninkov M, Popov-Aleksandrov A, Demenesku J, Mirkov I, Mileusnić D, Petrović A, Grigorov I, Zolotarevski L, Tolinački M, Kataranovski D, Brčeski I, Kataranovski M. Toxicity of oral cadmium intake: Impact on gut immunity. in Toxicology Letters. 2015;237(2):89-99.
doi:10.1016/j.toxlet.2015.06.002 .

Ninkov, Marina, Popov-Aleksandrov, Aleksandra, Demenesku, Jelena, Mirkov, Ivana, Mileusnić, Dina, Petrović, Anja, Grigorov, Ilijana, Zolotarevski, Lidija, Tolinački, Maja, Kataranovski, Dragan, Brčeski, Ilija, Kataranovski, Milena, "Toxicity of oral cadmium intake: Impact on gut immunity" in Toxicology Letters, 237, no. 2 (2015):89-99,
https://doi.org/10.1016/j.toxlet.2015.06.002 . .