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

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.

Meldonium Supplementation in Professional Athletes: Career Destroyer or Lifesaver?

“…The anti-inflammatory effect of meldonium was studied in a rat model of LPS-induced sepsis. Administration of meldonium at a dose of 300 mg/kg bw/day for four weeks before inducing sepsis in animals showed an increased activity of tissue copper-zinc SOD, manganese SOD, catalase (CAT), and glutathione peroxidase (GSH-Px) and reduced levels of lipid peroxidation, TNFα, phospho-nuclear factor kappa B p65 form (p-NF-κB p65), and the Bax/Bcl-2 apoptotic marker ratio, suggesting the anti-inflammatory and anti-apoptotic effects of meldonium [ 31 , 32 ]. Studies on the administration of meldonium to carnivorous fish show a decrease in the gene expression of proinflammatory molecules (IL1β and TNFα) and apoptotic molecules (Caspase 3 and 9) in the liver [ 24 , 33 ].…”

“…All these studies demonstrate that meldonium can be considered an effective therapeutic approach in preventing MD and impaired energy homeostasis [ 8 , 32 ].…”

Influence of Nitrogen-Modified Atmosphere Storage on Lipid Oxidation of Peanuts: From a Lipidomic Perspective

“…Lipidomics was a branch of metabolomics that allowed the characterizing and quantifying of lipids in biological samples [14]. In recent years, lipidomics based on LC-MS technology have been widely used in the analysis of various oil-rich products owing to their high separation capacity, high throughput, high sensitivity, and high resolution [15].…”