ArticleInternational journal of molecular sciences2024
M6229 Protects against Extracellular-Histone-Induced Liver Injury, Kidney Dysfunction, and Mortality in a Rat Model of Acute Hyperinflammation.
Article in International journal of molecular sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07285603 (A Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of M6229 Administered as a 120-hour Continuous Infusion at Three Sequential Dose Levels Versus Placebo in Healthy Subjects), which is not on this map. Cited by 6 papers.
What it found
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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.
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.
A Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of M6229 Administered as a 120-hour Continuous Infusion at Three Sequential Dose Levels Versus Placebo in Healthy Subjects
Who cites it
6 citing papers in PubMed, 8 citations in OpenAlex.
- Emerging biomodels to understand the pathophysiology of sepsis and evaluate new therapeutic strategies targeting extracellular histones.Materials today. Bio · 2026Review
- Circulating histones as clinical biomarkers in critically ill conditions.FEBS letters · 2025Review
- A phase I trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenously administered low-anticoagulant heparin (M6229) in critically ill sepsis patients.Intensive care medicine experimental · 2025Article
- "The NET effect": Neutrophil extracellular traps-a potential key component of the dysregulated host immune response in sepsis.Critical care (London, England) · 2025Review
- The Preventive and Therapeutic Effects of Acute and Severe Inflammatory Disorders with Heparin and Heparinoid.Biomolecules · 2024Review
- Emerging therapeutic strategies targeting extracellular histones for critical and inflammatory diseases: an updated narrative review.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extracellular histones have been shown to act as DAMPs in a variety of inflammatory diseases. Moreover, they have the ability to induce cell death. In this study, we show that M6229, a low-anticoagulant fraction of unfractionated heparin (UFH), rescues rats that were challenged by continuous infusion of calf thymus histones at a rate of 25 mg histones/kg/h. Histone infusion by itself induced hepatic and homeostatic dysfunction characterized by elevated activity of hepatic enzymes (ASAT and ALAT) and serum lactate levels as well as by a renal dysfunction, which contributed to the significantly increased mortality rate. M6229 was able to restore normal levels of both hepatic and renal parameters at 3 and 9 mg M6229/kg/h and prevented mortality of the animals. We conclude that M6229 is a promising therapeutic agent to treat histone-mediated disease.
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Registered trials
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 OpenQuestion graph.