Anserine reduces mortality in experimental sepsis by preventing methylglyoxal-induced capillary leakage.

Summary

Using clinical data analyses, animal models, and mechanistic in vitro assays, the study shows methylglyoxal drives endothelial barrier failure and capillary leak in sepsis via RAGE–MAPK signaling. The dipeptide anserine scavenges methylglyoxal, preserves junctional integrity, reduces capillary leakage, and lowers mortality in vivo.

Key Findings

• Methylglyoxal independently associated with 48-hour mortality and higher catecholamine/fluids in early sepsis.
• Carbonyl stress disrupted endothelial junctional proteins causing capillary leak in murine sepsis models.
• RAGE–MAPK signaling mediated the detrimental effects of methylglyoxal.
• Anserine reduced AGE formation, preserved junctional complexes in vitro, and decreased capillary leakage and mortality in vivo.

Clinical Implications

If validated in humans, anserine or other methylglyoxal-scavenging strategies could reduce vasopressor/fluids needs and improve survival in septic shock by stabilizing the endothelial barrier.

Limitations

• Preclinical efficacy; no randomized human interventional data yet.
• Exact human sample sizes and selection from the secondary analyses are not detailed in the abstract.

Future Directions

Conduct early-phase clinical trials testing anserine or similar scavengers in septic shock with endothelial leak biomarkers to validate efficacy and dosing.