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Article

The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats

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Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia
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Faculty of Chemistry, University of Belgrade, 11000 Belgrade, Serbia
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Institute of General and Physical Chemistry, University of Belgrade, 11000 Belgrade, Serbia
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School of Medicine, University of Belgrade, 11000 Belgrade, Serbia
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Vinča Institute of Nuclear Sciences—National Institute of Serbia, University of Belgrade, 11000 Belgrade, Serbia
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Centre for Medical Biochemistry, University Clinical Centre of Serbia, 11000 Belgrade, Serbia
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Faculty of Medical Sciences, University of Kragujevac, 550601 Kragujevac, Serbia
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University Medical Centre “Bežanijska Kosa”, 11080 Belgrade, Serbia
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Author to whom correspondence should be addressed.
Academic Editor: Guido R.M.M. Haenen
Int. J. Mol. Sci. 2022, 23(4), 2395; https://doi.org/10.3390/ijms23042395
Received: 26 December 2021 / Revised: 9 February 2022 / Accepted: 14 February 2022 / Published: 21 February 2022
(This article belongs to the Collection Feature Papers in Molecular Toxicology)
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. View Full-Text
Keywords: sepsis; liver; kidney; heart; inflammation; oxidative stress; lipidomics; rats sepsis; liver; kidney; heart; inflammation; oxidative stress; lipidomics; rats
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MDPI and ACS Style

Đurašević, S.; Ružičić, A.; Lakić, I.; Tosti, T.; Đurović, S.; Glumac, S.; Pejić, S.; Todorović, A.; Drakulić, D.; Stanković, S.; Jasnić, N.; Đorđević, J.; Todorović, Z. The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats. Int. J. Mol. Sci. 2022, 23, 2395. https://doi.org/10.3390/ijms23042395

AMA Style

Đurašević S, Ružičić A, Lakić I, Tosti T, Đurović S, Glumac S, Pejić S, Todorović A, Drakulić D, Stanković S, Jasnić N, Đorđević J, Todorović Z. The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats. International Journal of Molecular Sciences. 2022; 23(4):2395. https://doi.org/10.3390/ijms23042395

Chicago/Turabian Style

Đurašević, Siniša, Aleksandra Ružičić, Iva Lakić, Tomislav Tosti, Saša Đurović, Sofija Glumac, Snežana Pejić, Ana Todorović, Dunja Drakulić, Sanja Stanković, Nebojša Jasnić, Jelena Đorđević, and Zoran Todorović. 2022. "The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats" International Journal of Molecular Sciences 23, no. 4: 2395. https://doi.org/10.3390/ijms23042395

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