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.

Evaluate if O-GlcNAc stimulation could improve sepsis outcomes in young.

Endotoxemic shock was induced in 28 days old rats with an i.v. injection of saline (CTRL) or LPS (O111:B4, 20mg.kg⁻¹ – LPS). 1hour after LPS rats were randomly assigned to no therapy (LPS), fluidotherapy (saline, 10mL.kg⁻¹ – LPS+R)±NButGT (10mg.kg⁻¹ – NButGT) to increase O-GlcNAc levels. 2hours 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.

LPS induced a shock (mean arterial pressure (MAP): CTRL: 67.2±1.9; LPS: 50.7±2.1; mmHg; P<0.05), altered biological parameters (lactates: CTRL: 3.92±0.26; LPS: 6.42±0.45; mmol.L⁻¹; troponin T: CTRL: 19.7±4.0; LPS: 45.4±11.4; ng.L⁻¹; P<0.05) and PRISM score (P<0.05). LPS+R had no beneficial effect while NButGT improves MAP (P<0.05), PRISM score (P<0.05) and the median survival (NButGT: 36.0; LPS+R: 13.65; hours; P<0.001) compared to LPS+R treatment.

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.