O-GlcNAc levels stimulation improves survival at the early phase of septic shock in the young

Background We have shown that increase in O-GlcNAc levels, a post-translational modification, at the early phase of septic shock in adult (84 days old rats) resulted in a 3-fold increase in survival time. Most studies focus only in adults, and the population most affected by septic shock, young children, is rarely studied. Sepsis, with a mortality rate of 29%, is an important but preventable cause of pediatric death worldwide. Considering that basal O-GlcNAc levels are higher in the young, the potential impact of O-GlcNAc stimulation at the early phase of septic shock in the young should be evaluated. Purpose Evaluate if O-GlcNAc stimulation could improve sepsis outcomes in young. Methods Endotoxemic shock was induced in 28 days old rats with an i.v. injection of saline (CTRL) or LPS (O111:B4, 20 mg.kg−1 – LPS). 1 hour after LPS rats were randomly assigned to no therapy (LPS), fluidotherapy (saline, 10 mL.kg−1 – LPS + R) ± NButGT (10 mg.kg−1 – NButGT) to increase O-GlcNAc levels. 2 hours later, physiological functions and plasmatic markers were measured and used in adapted Pediatric RISk of Mortality score (PRISM score). The impact of treatment on survival was evaluated on n = 64. Results LPS induced a shock (mean arterial pressure (MAP): CTRL: 67.2 ± 1.9; LPS: 50.7 ± 2.1; mmHg; P  Conclusion Despite higher O-GlcNAc levels in young population, we demonstrate that O-GlcNAc stimulation is able to improve pups’ response to endotoxemic shock. Our results show that it is the difference in O-GlcNAcylation between the basal levels and the post-stimulation levels that induces protection against septic shock.