Evaluating 2‐0, 3‐1 Desulfated Heparin (ODSH) Dosing for Radiation Combined Burn Injury

Abstract

Victims of radiation events succumb to serious infections as a consequence of bacterial translocation and sepsis. Exacerbation of the risk of infection by radiation combined burn injury (RCBI) further heightens vulnerability. No suitable countermeasures for RCBI exist. We evaluated ODSH, an anticoagulant and anti‐inflammatory agent as a potential countermeasure to RCBI. Female mice (12‐week, B6D2F1/J) were subjected to 9.5 Gy (LD70/30 for RCBI) whole‐body bilateral 60Co gamma‐photon radiation (0.4 Gy/min), followed by dorsal skin burn injury under anesthesia (∼15% total‐body‐surface area burn). Mice were injected (S.C.) with ODSH (25 mg/kg every 12 h; days 1‐2 and 17.5 mg/kg every 12 h; days 3‐7) or vehicle for 7 days post‐injury and further administered topical gentamicin (0.1% cream; days 1‐10) and oral levofloxacin (100 mg/kg; days 3‐16). Mice were euthanized on day 30 following water consumption, body weight and survival analysis. Our data showed ODSH had no effect on radiation injury (RI)‐induced mortality (45% ODSH vs. 45% VEH; n = 20). Interestingly ODSH treatment significantly reduced survival after RCBI (12% ODSH vs. 41% VEH; n = 22). Furthermore, ODSH did not affect water consumption or body mass after RI or RCBI. ODSH also did not counteract the negative alterations in hematology, splenocytes, or bone marrow cell counts after RI or RCBI. These data illustrate that ODSH in combination with antibiotic treatments, may not be a mitigating countermeasure for RCBI. This work was supported by NIAID Grant G1B2265014.

Medicinal Thiols: Current Status and New Perspectives

“…By slowing proliferation, these agents effectively allow more time for DNA repair in important progenitor cells and may, therefore, be beneficial in accelerating the recovery of blood cell populations. In a mouse model of radiation exposure complicated by severe skin burns, however, captopril actually reduced survival [139]. This scenario can be particularly challenging, as depletion of immune cell populations greatly increases the risk of infection and slows wound healing in these patients [140].…”

“…Radioprotection [113,119,[121][122][123][124][125][126][127][128][129][130][131][132][133][134] Scavenges free radicals formed during RT -Captopril Hypertension [163,[165][166] Blocks activation of angiotensin, a vasoconstrictor Lead toxicity [89] Radioprotection [136][137][138][139] Metallo-β-lactamase inhibition [167][168][169] Alzheimer's/dementia [173,174] Dimercaprol, BAL in oil Heavy metal toxicity As, Au, Hg, and Pb [71][72][94][95][96] Chelates heavy metals, facilitating their removal -2,3-meso-Dimercaptosuccinic acid…”