The effects of a meldonium pre-treatment on the course of the faecal-induced sepsis in rats
2021
Authors:
Đurašević, SinišaRužičić, Aleksandra
Lakić, Iva
Tosti, Tomislav
Đurović, Saša
Glumac, Sofija
Pavlović, Slađan
Borković Mitić, Slavica
Grigorov, Ilijana
Stanković, Sanja
Jasnić, Nebojša
Đorđević, Jelena
Todorović, Zoran
Document Type:
Article (Published version)
Metadata
Show full item recordAbstract:
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.
Keywords:
Sepsis; Liver; Kidney; Heart; Inflammation; Oxidative stress; Lipidomics; RatsSource:
International Journal of Molecular Sciences, 2021, 22, 18, 9698-Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200178 (University of Belgrade, Faculty of Biology) (RS-MESTD-inst-2020-200178)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200168 (University of Belgrade, Faculty of Chemistry) (RS-MESTD-inst-2020-200168)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200110 (University of Belgrade, Faculty of Medicine) (RS-MESTD-inst-2020-200110)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200051 (Institute of General and Physical Chemistry, Belgrade) (RS-MESTD-inst-2020-200051)
DOI: 10.3390/ijms22189698
ISSN: 1422-0067