From Molecular Mechanisms to Clinical Therapy: Understanding Sepsis-Induced Multiple Organ Dysfunction.
Tijana SrdićSinisa DjurasevicIva V LakicAleksandra A RuzicicPredrag Z VujovicTanja V JevdjovicTamara B DakicJelena ĐorđevićTomislav B TostiSofija GlumacZoran TodorovicNebojsa JasnicPublished in: International journal of molecular sciences (2024)
Sepsis-induced multiple organ dysfunction arises from the highly complex pathophysiology encompassing the interplay of inflammation, oxidative stress, endothelial dysfunction, mitochondrial damage, cellular energy failure, and dysbiosis. Over the past decades, numerous studies have been dedicated to elucidating the underlying molecular mechanisms of sepsis in order to develop effective treatments. Current research underscores liver and cardiac dysfunction, along with acute lung and kidney injuries, as predominant causes of mortality in sepsis patients. This understanding of sepsis-induced organ failure unveils potential therapeutic targets for sepsis treatment. Various novel therapeutics, including melatonin, metformin, palmitoylethanolamide (PEA), certain herbal extracts, and gut microbiota modulators, have demonstrated efficacy in different sepsis models. In recent years, the research focus has shifted from anti-inflammatory and antioxidative agents to exploring the modulation of energy metabolism and gut microbiota in sepsis. These approaches have shown a significant impact in preventing multiple organ damage and mortality in various animal sepsis models but require further clinical investigation. The accumulation of this knowledge enriches our understanding of sepsis and is anticipated to facilitate the development of effective therapeutic strategies in the future.
Keyphrases
- oxidative stress
- septic shock
- acute kidney injury
- intensive care unit
- diabetic rats
- anti inflammatory
- heart failure
- small molecule
- high glucose
- left ventricular
- type diabetes
- risk assessment
- cardiovascular disease
- newly diagnosed
- ejection fraction
- heat shock
- replacement therapy
- combination therapy
- smoking cessation
- extracorporeal membrane oxygenation