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Recombinant Thrombomodulin (Solulin) Ameliorates Early Intestinal Radiation Toxicity in a Preclinical Rat Model

Year: 2016
Type: article
Abstract: Intestinal radiation toxicity occurs during and after abdominopelvic radiotherapy. Endothelial cells play a significant role in modulating radiation-induced intestinal damage. We demonstrated that the endothelial cell surface receptor thrombomodulin (TM), a protein with anticoagulant, anti-inflammatory and antioxidant properties, mitigates radiation-induced lethality in mice. The goal of this study was to determine whether recombinant TM (Solulin) can protect the intestine from toxicity in a clinically relevant rat model. A 4 cm loop of rat small bowel was exposed to fractionated 5 Gy X radiation for 9 consecutive days. The animals were randomly assigned to receive daily subcutaneous injections of vehicle or Solulin (3 mg/kg/day or 10 mg/kg/day) for 27 days starting 4 days before irradiation. Early intestinal injury was assessed two weeks after irradiation by quantitative histology, morphometry, immunohistochemistry and luminol bioluminescence imaging. Solulin treatment significantly ameliorated intestinal radiation injury, made evident by a decrease in myeloperoxidase (MPO) activity, transforming growth factor beta (TGF-β) immunoreactivity, collagen-I deposition, radiation injury score (RIS) and intestinal serosal thickening. These findings indicate the need for further development of Solulin as a prophylactic and/or therapeutic agent to mitigate radiation-induced intestinal damage.
DOI: 10.1667/rr14408.1
Authors: Rupak Pathak, Junru Wang, Sarita Garg, Nukhet Aykin-Burns, Karl-Uwe Petersen, Martin Hauer-Jensen
Language: English
Field: Medicine
Open Access status: green
Funders: National Aeronautics and Space Administration, Arkansas Space Grant Consortium, National Space Biomedical Research Institute, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences
Awards: ARKANSAS NASA EPSCOR PLANS TO: CONTINUE TO FUND THE NASA EPSCOR PROGRAM OFFICE TO ENSURE CONTINUED MOMENTUM AND GOOD PROGRESS IN NASA RELEVANT AEROSP, Molecular Pathogenesis of Radiation Enteropathy, Center for Studies of Host Response to Cancer Therapy, G5665650313, G690245692, NATIONAL SPACE BIOMEDICAL RESEARCH INSTITUTE, G816501378, G8392571047, G9000037057, G9000106993
OpenAlex ID: W2480800001
FWCI: 2.008
Cites: 59
Cited by: 16
Related to: 10