TY  - JOUR
AU  - Ðurašević, Siniša
AU  - Ružičić, Aleksandra
AU  - Lakić, Iva
AU  - Tosti, Tomislav
AU  - Ðurović, Saša
AU  - Glumac, Sofija
AU  - Pejić, Snežana
AU  - Todorović, Ana
AU  - Drakulić, Dunja
AU  - Stanković, Sanja
AU  - Jasnić, Nebojša
AU  - Dević, Jelena Ð.
AU  - Todorović, Zoran B.
PY  - 2022
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5076
AB  - A dysregulated and overwhelming response to an infection accompanied by the exaggerated pro-inflammatory state and metabolism disturbance leads to the fatal outcome in sepsis. Previously we showed that meldonium, an anti-ischemic drug clinically used to treat myocardial and cerebral ischemia, strongly increases mortality in faecal-induced peritonitis (FIP) in rats. We postulated that the same mechanism that is responsible for the otherwise strong anti-inflammatory effects of meldonium could be the culprit of the increased mortality. In the present study, we applied the LPS-induced model of sepsis to explore the presence of any differences from and/or similarities to the FIP model. When it comes to energy production, despite some shared similarities, it is evident that LPS and FIP models of sepsis differ greatly. A different profile of sympathoadrenal activation may account for this observation, as it was lacking in the FIP model, whereas in the LPS model it was strong enough to overcome the effects of meldonium. Therefore, choosing the appropriate model of sepsis induction is of great importance, especially if energy homeostasis is the main focus of the study. Even when differences in the experimental design of the two models are acknowledged, the role of different patterns of energy production cannot be excluded. On that account, our results draw attention to the importance of uninterrupted energy production in sepsis but also call for much-needed revisions of the current recommendations for its treatment. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PB  - MDPI
T2  - International Journal of Molecular Sciences
T1  - The Effects of a Meldonium Pre-Treatment on the Course of the
LPS-Induced Sepsis in Rats
VL  - 23
IS  - 4
DO  - 10.3390/ijms23042395
ER  - 

@article{
author = "Ðurašević, Siniša and Ružičić, Aleksandra and Lakić, Iva and Tosti, Tomislav and Ðurović, Saša and Glumac, Sofija and Pejić, Snežana and Todorović, Ana and Drakulić, Dunja and Stanković, Sanja and Jasnić, Nebojša and Dević, Jelena Ð. and Todorović, Zoran B.",
year = "2022",
abstract = "A dysregulated and overwhelming response to an infection accompanied by the exaggerated pro-inflammatory state and metabolism disturbance leads to the fatal outcome in sepsis. Previously we showed that meldonium, an anti-ischemic drug clinically used to treat myocardial and cerebral ischemia, strongly increases mortality in faecal-induced peritonitis (FIP) in rats. We postulated that the same mechanism that is responsible for the otherwise strong anti-inflammatory effects of meldonium could be the culprit of the increased mortality. In the present study, we applied the LPS-induced model of sepsis to explore the presence of any differences from and/or similarities to the FIP model. When it comes to energy production, despite some shared similarities, it is evident that LPS and FIP models of sepsis differ greatly. A different profile of sympathoadrenal activation may account for this observation, as it was lacking in the FIP model, whereas in the LPS model it was strong enough to overcome the effects of meldonium. Therefore, choosing the appropriate model of sepsis induction is of great importance, especially if energy homeostasis is the main focus of the study. Even when differences in the experimental design of the two models are acknowledged, the role of different patterns of energy production cannot be excluded. On that account, our results draw attention to the importance of uninterrupted energy production in sepsis but also call for much-needed revisions of the current recommendations for its treatment. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.",
publisher = "MDPI",
journal = "International Journal of Molecular Sciences",
title = "The Effects of a Meldonium Pre-Treatment on the Course of the
LPS-Induced Sepsis in Rats",
volume = "23",
number = "4",
doi = "10.3390/ijms23042395"
}

Ðurašević, S., Ružičić, A., Lakić, I., Tosti, T., Ðurović, S., Glumac, S., Pejić, S., Todorović, A., Drakulić, D., Stanković, S., Jasnić, N., Dević, J. Ð.,& Todorović, Z. B.. (2022). The Effects of a Meldonium Pre-Treatment on the Course of the
LPS-Induced Sepsis in Rats. in International Journal of Molecular Sciences
MDPI., 23(4).
https://doi.org/10.3390/ijms23042395

Ðurašević S, Ružičić A, Lakić I, Tosti T, Ðurović S, Glumac S, Pejić S, Todorović A, Drakulić D, Stanković S, Jasnić N, Dević JÐ, Todorović ZB. The Effects of a Meldonium Pre-Treatment on the Course of the
LPS-Induced Sepsis in Rats. in International Journal of Molecular Sciences. 2022;23(4).
doi:10.3390/ijms23042395 .

Ðurašević, Siniša, Ružičić, Aleksandra, Lakić, Iva, Tosti, Tomislav, Ðurović, Saša, Glumac, Sofija, Pejić, Snežana, Todorović, Ana, Drakulić, Dunja, Stanković, Sanja, Jasnić, Nebojša, Dević, Jelena Ð., Todorović, Zoran B., "The Effects of a Meldonium Pre-Treatment on the Course of the
LPS-Induced Sepsis in Rats" in International Journal of Molecular Sciences, 23, no. 4 (2022),
https://doi.org/10.3390/ijms23042395 . .

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 . .