Serum histones as biomarkers of the severity of heatstroke in dogs

Yaron Bruchim*, Isaac Ginsburg, Gilad Segev, Ahmad Mreisat, Yochai Avital, Itamar Aroch, Michal Horowitz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Heatstroke is associated with systemic inflammatory response syndrome, leading to multiple organ dysfunction and death. Currently, there is no specific treatment decreasing hyperthermia-induced inflammatory/hemostatic derangements. Emerging studies indicate that histones leaking from damaged cells into the extracellular space are toxic, pro-inflammatory, and pro-thrombotic. We therefore hypothesize that serum histones (sHs) are elevated during heatstroke and are associated with the severity of the disease. Sixteen dogs with heatstroke and seven healthy controls were included in the study. Median serum histones (sHs) upon admission in dogs with heatstroke were significantly higher (P = 0.043) compared to that in seven controls (13.2 vs. 7.3 ng/mL, respectively). sHs level was significantly higher among non-survivors and among dogs with severe hemostatic derangement (P = 0.049, median 21.4 ng/mL vs. median 8.16 ng/mL and P = 0.038, 19.0 vs. 7.0 ng/mL, respectively). There were significant positive correlation between sHs and urea (r = 0.8, P = 0.02); total CO2 (r = 0.661, P = 0.05); CK (r = 0.678, P = 0.04); and prothrombin time (PT) 12 h post presentation (r = 0.888, P = 0.04). The significant positive correlation between sHs and other heatstroke severity biomarkers, and significant increase among severely affected dogs, implies its role in inflammation/oxidation/coagulation during heatstroke. sHs, unlike other prognostic and severity biomarkers in heatstroke, can be pharmacologically manipulated, offering a potential therapeutic target.

Original languageAmerican English
Pages (from-to)903-910
Number of pages8
JournalCell Stress and Chaperones
Issue number6
StatePublished - 1 Nov 2017

Bibliographical note

Publisher Copyright:
© 2017, Cell Stress Society International.


  • Canine
  • Hemostatic
  • Heparin
  • Inflammation
  • Protein C


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