The Novel Compound SUL-138 Counteracts Endothelial Cell and Kidney Dysfunction in Sepsis by Preserving Mitochondrial Function.

Sepsis is defined as a dysregulated host response leading to organ dysfunction, which may ultimately result in the patient's death. Mitochondrial dysfunction plays a key role in developing organ dysfunction in sepsis. In this study, we explored the efficacy of the novel mitochondrial protective compound, SUL-138, in sepsis models in HUVECs and mice.

GYY4137-Derived Hydrogen Sulfide Donates Electrons to the Mitochondrial Electron Transport Chain via Sulfide: Quinone Oxidoreductase in Endothelial Cells.

The protective effects of hydrogen sulphide (HS) to limit oxidative injury and preserve mitochondrial function during sepsis, ischemia/reperfusion, and neurodegenerative diseases have prompted the development of soluble HS-releasing compounds such as GYY4137. Yet, the effects of GYY4137 on the mitochondrial function of endothelial cells remain unclear, while this cell type comprises the first target cell after parenteral administration. Here, we specifically assessed whether human endothelial cells possess a functional sulfide:quinone oxidoreductase (SQOR), to oxidise GYY4137-released HS within the mitochondria for electron donation to the electron transport chain.

Association between oxidized nucleobases and mitochondrial DNA damage with long-term mortality in patients with sepsis.

Background: Sepsis not only leads to short-term mortality during hospitalization, but is also associated with increased mortality during long-term follow-up after hospital discharge. Metabolic stress during sepsis may cause oxidative damage to both nuclear and mitochondrial DNA (mtDNA) and RNA, which could affect long-term health and life span. Therefore, the aim of this study was to assess the association of sepsis with oxidized nucleobases and (mt)DNA damage and long-term all-cause mortality in septic patients.

Sepsis is associated with mitochondrial DNA damage and a reduced mitochondrial mass in the kidney of patients with sepsis-AKI.

Background: Sepsis is a life-threatening condition accompanied by organ dysfunction subsequent to a dysregulated host response to infection. Up to 60% of patients with sepsis develop acute kidney injury (AKI), which is associated with a poor clinical outcome. The pathophysiology of sepsis-associated AKI (sepsis-AKI) remains incompletely understood, but mitochondria have emerged as key players in the pathogenesis.

A high urea-to-creatinine ratio predicts long-term mortality independent of acute kidney injury among patients hospitalized with an infection.

Acute kidney injury (AKI) occurs frequently in patients with sepsis. Persistent AKI is, in contrast to transient AKI, associated with reduced long-term survival after sepsis, while the effect of AKI on survival after non-septic infections remains unknown. As prerenal azotaemia is a common cause of transient AKI that might be identified by an increased urea-to-creatinine ratio, we hypothesized that the urea-to-creatinine ratio may predict the course of AKI with relevance to long-term mortality risk.

Metabolic Resuscitation Strategies to Prevent Organ Dysfunction in Sepsis.

Sepsis is the main cause of death among patients admitted to the intensive care unit. As current treatment is limited to antimicrobial therapy and supportive care, mortality remains high, which warrants efforts to find novel therapies. Mitochondrial dysfunction is emerging as a key process in the induction of organ dysfunction during sepsis, and metabolic resuscitation might reveal to be a novel cornerstone in the treatment of sepsis.