Abstract
Septic shock is a systemic inflammation associated with cell metabolism disorders and cardiovascular dysfunction. Increases in O-GlcNAcylation have shown beneficial cardiovascular effects in acute pathologies. We used two different rat models to evaluate the beneficial effects of O-GlcNAc stimulation at the early phase of septic shock. Rats received lipopolysaccharide (LPS) to induce endotoxemic shock or saline (control) and fluid resuscitation (R) with or without O-GlcNAc stimulation (NButGT–10 mg/kg) 1 hour after shock induction. For the second model, rats received cecal ligature and puncture (CLP) surgery and fluid therapy with or without NButGT. Cardiovascular function was evaluated and heart and blood samples were collected and analysed. NButGT treatment efficiently increased total O-GlcNAc without modification of HBP enzyme expression.Treatment improved circulating parameters and cardiovascular function in both models, and restored SERCA2a expression levels. NButGT treatment also reduced animal mortality. In this study, we demonstrate that in septic shock O-GlcNAc stimulation improves global animal and cardiovascular function outcomes associated with a restoration of SERCA2a levels. This pre-clinical study opens avenues for a potential therapy of early-stage septic shock.
Highlights
Septic shock is a systemic inflammation associated with cell metabolism disorders and cardiovascular dysfunction
We propose that an increase in protein O-GlcNAcylation by NButGT post-treatment could improve the outcome of septic shock in an animal model., We demonstrate that despite no improvement in the inflammatory state, increased protein O-GlcNAcylation improves global outcome in our septic shock rats
NButGT efficiently increases total O-GlcNAc in septic shock without any consequence on major enzymes involved in the hexosamine biosynthetic pathway
Summary
Septic shock is a systemic inflammation associated with cell metabolism disorders and cardiovascular dysfunction. The level of O-GlcNAcylated proteins and HBP enzymes (OGT and OGA) were not modified when compared to control or Sham rat samples (Fig. 1), but an increase in GFAT, the limiting rate enzyme (p = 0.0210 vs Sham Fig. 2B) was observed in the CLP model. NButGT supplementation in the fluid resuscitation to stimulate protein O-GlcNAcylation did not further impact the mean arterial pressure (similar to the control and LPS + R group).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
