Combined therapy with gas gangrene antitoxin and recombinant human soluble thrombomodulin for Clostridium perfringens sepsis in a rat model

Toxicon. 2018 Jan:141:112-117. doi: 10.1016/j.toxicon.2017.12.043. Epub 2017 Dec 12.

Abstract

Cases of Clostridium perfringens septicemia, such as liver abscess, often develop a rapidly progressive intravascular hemolysis and coagulation; the mortality rate with current standard care including antibiotics and surgery is high. Herein, we firstly investigated the effects of gas gangrene antitoxin (GGA) (antitoxin against C. perfringens) and recombinant human soluble thrombomodulin (rTM) on the hemolysis, coagulation status, inflammatory process, and mortality in α-toxin-treated rats. Male 11-week-old Sprague Dawley rats were randomly divided into five groups: control group, α-toxin group, GGA group, rTM group, and combined GGA and rTM (combination group). After α-toxin injection, mortality and platelet counts, and hemolysis were observed for 6 h. The fibrin/fibrinogen degradation products (FDP), and plasma high-mobility group box 1 (HMGB1) were also measured at 6 h. The combination group demonstrated 100% survival compared with 50% survival in the α-toxin group and demonstrated significantly improved hemolysis, platelet counts, and lactate levels compared with those in the α-toxin group (p < .01). The FDP and HMGB1 levels in the combination therapy group were significantly lower than those in the α-toxin group (p < .05). Combination therapy with GGA and rTM administration is applicable as adjunct therapy for fatal C. perfringens sepsis.

Keywords: Clostridium perfringens; Gas gangrene antitoxin; Hemolysis; Recombinant human soluble thrombomodulin; Sepsis.

MeSH terms

  • Animals
  • Antitoxins / pharmacology*
  • Bacterial Toxins
  • Clostridium perfringens / pathogenicity*
  • Fibrin Fibrinogen Degradation Products
  • Gas Gangrene / immunology*
  • HMGB1 Protein
  • Hemolysis / drug effects
  • Male
  • Platelet Count
  • Rats, Sprague-Dawley
  • Recombinant Proteins
  • Sepsis / drug therapy*
  • Sepsis / immunology
  • Thrombomodulin / therapeutic use*

Substances

  • Antitoxins
  • Bacterial Toxins
  • Fibrin Fibrinogen Degradation Products
  • HMGB1 Protein
  • Recombinant Proteins
  • THBD protein, human
  • Thrombomodulin