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

International Journal of Molecular Sciences

Sanja Stanković¹  Siniša Đurašević²  Iva Lakić²  Jelena Đorđević²  Nebojša Jasnić²  Aleksandra Ružičić²  Tomislav Tosti³  Slađan Pavlović⁴  Ilijana Grigorov⁴  Slavica Borković-Mitić⁴  Saša Đurović⁵  Sofija Glumac⁶  Zoran Todorović⁶ 

[1] Centre for Medical Biochemistry, University Clinical Centre of Serbia, 11000 Belgrade, Serbia;Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia;Faculty of Chemistry, University of Belgrade, 11000 Belgrade, Serbia;Institute for Biological Research “Siniša Stanković”—National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia;Institute of General and Physical Chemistry, University of Belgrade, 11000 Belgrade, Serbia;School of Medicine, University of Belgrade, 11000 Belgrade, Serbia;

关键词: sepsis;    liver;    kidney;    heart;    inflammation;    oxidative stress;   

DOI  :  10.3390/ijms22189698

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown