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 . .