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.
Original language | English |
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Article number | 1376 |
Journal | International journal of molecular sciences |
Volume | 25 |
Issue number | 3 |
DOIs | |
Publication status | Published - 1 Feb 2024 |
Keywords
- DAMPs
- M6229
- extracellular histones
- hyperinflammation
- organ injury
- rat model
- sepsis