Evidence map›Paper›PMID 40107203›Full record

ArticleEBioMedicine2025

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

Thomas Schmoch, Nadia Gallenstein, Verena Peters, Maria Bartosova, Florian Uhle, Laura Kummer, Anian Mair, Ute Krauser, Manuel Feisst, Peter P Nawroth and 3 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Thomas SchmochDepartment of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany; Medical Faculty Heidelberg, Department of Anesthesiology, Heidelberg University, Heidelberg, Germany; Department of Anesthesiology and Intensive Care Medicine, Hôpitaux Robert Schuman - Hôpital Kirchberg, Luxembourg City, Luxembourg. Electronic address: thomas.schmoch@uk-essen.de.
Nadia GallensteinMedical Faculty Heidelberg, Department of Anesthesiology, Heidelberg University, Heidelberg, Germany. Electronic address: nadia.gallenstein@med.uni-heidelberg.de.
Verena PetersMedical Faculty Heidelberg, Department of Pediatrics I, Center for Paediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany.
Maria BartosovaMedical Faculty Heidelberg, Department of Pediatrics I, Center for Paediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany.
Florian UhleMedical Faculty Heidelberg, Department of Anesthesiology, Heidelberg University, Heidelberg, Germany.
Laura KummerMedical Faculty Heidelberg, Department of Anesthesiology, Heidelberg University, Heidelberg, Germany.
Anian MairMedical Faculty Heidelberg, Department of Anesthesiology, Heidelberg University, Heidelberg, Germany.
Ute KrauserMedical Faculty Heidelberg, Department of Anesthesiology, Heidelberg University, Heidelberg, Germany.
Manuel FeisstInstitute of Medical Biometry, Heidelberg University, Heidelberg, Germany.
Peter P NawrothMedical Faculty Heidelberg, Department of Medicine I and Clinical Chemistry, Heidelberg University, Heidelberg, Germany.
Markus A WeigandMedical Faculty Heidelberg, Department of Anesthesiology, Heidelberg University, Heidelberg, Germany.
Claus Peter SchmittMedical Faculty Heidelberg, Department of Pediatrics I, Center for Paediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany.
Thorsten BrennerDepartment of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany; Medical Faculty Heidelberg, Department of Anesthesiology, Heidelberg University, Heidelberg, Germany. Electronic address: Thorsten.Brenner@uk-essen.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundWe previously identified methylglyoxal as a biomarker for early identification and outcome prediction in human sepsis. We hypothesised that methylglyoxal causally impacts disease severity, and the methylglyoxal-scavenging dipeptide anserine can attenuate the detrimental effects of methylglyoxal.

methodsUsing a translational approach, secondary analyses of two observational trials were performed to test the initial hypotheses. Afterwards, these results were re-evaluated in different murine models of experimental sepsis in vivo. The detrimental effects of methylglyoxal as well as the underlying mechanisms were further assessed in vitro using transendothelial electrical resistance measurements, fluorescence-activated cell sorting analyses, cytokine assays, gene expression analyses, and enzyme activity assays, as well as immunofluorescence and immunohistochemistry staining.

findingsThe secondary analyses confirmed methylglyoxal as an independent marker associated with increased mortality within the first 48 h after sepsis onset and high catecholamine and fluid requirements in the first 24 h after sepsis onset. In the sepsis models, methylglyoxal-derived carbonyl stress significantly contributed to the development of capillary leakage by disrupting endothelial barrier-forming proteins. Mechanistically, a pathway involving the receptor of advanced glycation end products and mitogen-activated protein kinase was identified. The methylglyoxal-scavenging dipeptide anserine (β-alanyl-N-methylhistidine) reduced methylglyoxal-induced advanced glycation end-product formation and disruptions of junctional complexes in vitro. Moreover, anserine reduced capillary leakage and mortality in vivo.

interpretationMethylglyoxal causally contributes to capillary leak formation and mortality in experimental sepsis, which can be mitigated by anserine. Therefore, anserine represents an innovative therapeutic option for the treatment of septic shock.

fundingGerman Research Foundation (grant number BR 4144/2-1).

Indexed as

AnserineCapillary PermeabilityPyruvaldehydeSepsisAnimalsBiomarkersDisease Models, AnimalHumansMaleMiceAnserineBiomarkersPyruvaldehydeAnserineCarbonyl stressReceptor of advanced glycation end products (RAGE)Septic shock

Identifiers

PMID40107203
PMCPMC11995882

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.