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

Autor: Saša Đurović, Tomislav Tosti, Sofija Glumac, Jelena Đorđević, Iva Lakic, Nebojša Jasnić, Siniša Đurašević, Slavica Borković-Mitić, Aleksandra Ružičić, Slađan Z. Pavlović, Ilijana Grigorov, Sanja Tanasković Stanković, Zoran Todorovic
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Anti-Inflammatory Agents
Apoptosis
Pharmacology
medicine.disease_cause
sepsis
Rats
Sprague-Dawley
Feces
Norepinephrine
0302 clinical medicine
Adrenal Glands
oxidative stress
Glycolysis
Biology (General)
Beta oxidation
Spectroscopy
Meldonium
0303 health sciences
Fatty Acids
Temperature
General Medicine
3. Good health
Computer Science Applications
Chemistry
Treatment Outcome
030220 oncology & carcinogenesis
medicine.symptom
medicine.drug
Methylhydrazines
kidney
Epinephrine
QH301-705.5
Inflammation
heart
liver
Catalysis
Article
Inorganic Chemistry
Sepsis
03 medical and health sciences
Troponin T
Animal mortality
medicine
Animals
Physical and Theoretical Chemistry
QD1-999
Molecular Biology
Triglycerides
030304 developmental biology
business.industry
Organic Chemistry
Lipid metabolism
medicine.disease
Lipid Metabolism
Rats
rats
Oxygen
inflammation
Lipidomics
lipidomics
Lipid Peroxidation
business
Oxidative stress
Biomarkers
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 18
International Journal of Molecular Sciences, Vol 22, Iss 9698, p 9698 (2021)
ISSN: 1422-0067
Popis: 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.
Databáze: OpenAIRE
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