Please use this identifier to cite or link to this item: https://biore.bio.bg.ac.rs/handle/123456789/4496
Title: The Effects of a Meldonium Pre-Treatment on the Course of the Faecal-Induced Sepsis in Rats
Authors: Đurašević, Siniša 
Ružičić, Aleksandra 
Lakić, Iva 
Tosti, Tomislav
Đurović, Saša
Glumac, Sofija
Pavlović, Slađan
Borković-Mitić, Slavica
Grigorov, Ilijana
Stanković, Sanja
Jasnić, Nebojša 
Đorđević, Jelena 
Todorović, Zoran.
Keywords: sepsis;liver;kidney;heart;inflammation;oxidative stress;lipidomics;rats
Issue Date: 8-Sep-2021
Rank: M21
Publisher: MDPI
Journal: International Journal of Molecular Sciences
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.
URI: https://biore.bio.bg.ac.rs/handle/123456789/4496
ISSN: 1422-0067
DOI: 10.3390/ijms22189698
Appears in Collections:Journal Article

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