Abstract
Radiation-induced acute intestinal injury after abdominal and pelvic irradiation is a common and serious problem in the clinical setting. Glucagon-like peptide-2 (GLP-2), a 33-amino acid peptide, exerts diverse effects related to the regulation of gastrointestinal growth and function. However, GLP-2 is relatively unstable in vivo. The aim of the present study was to improve GLP-2 stability in vivo and to evaluate its therapeutic effect on acute radiation enteritis. We generated long-lasting intestinal protection peptides by conjugating human GLP-2 (hGLP-2) peptides to polyethyleneglycol (PEG) to produce mPEGylation hGLP-2 (Mono-PEG-hGLP-2) through an enzymatic site-specific transglutamination reaction. Mono-PEG-hGLP-2 synthesized under optimal reaction conditions and separated by one-step ion-exchange chromatography was found to be resistant to degradation in vitro. Pretreatment with Mono-PEG-hGLP-2 reduced the severity of radiation-induced intestinal injury, oxidative stress, and the expression of NF-κB in rats with irradiation-induced acute radiation enteritis. The enhanced biological potency of Mono-PEG-hGLP-2 highlights its potential as a therapeutic agent for intestinal diseases.
Highlights
Radiotherapy is an important aspect of multimodal cancer therapy
Increased ratios of mPEG-SPA to pGLP-2 augmented the yield of MonoPEG-human GLP-2 (hGLP-2), but the yield was not increased until it reached a certain level
Increases in the molar ratio of mPEG-SPA resulted in multiple modification products; the conversion ratio of MonoPEG-hGLP-2 decreased
Summary
Radiotherapy is an important aspect of multimodal cancer therapy. Radiation-induced acute intestinal injury after abdominal and pelvic irradiation is a common and serious problem [1,2,3] that is progressive in nature, and in the clinic, it can result in symptoms such as nausea, vomiting and diarrhea. Radiotherapy can damage intestinal barrier function and induce changes in bacterial flora, vascular permeability of mucosal cells, and intestinal motility [1]. The morbidity and mortality due to radiation enterocolitis is high. Complications of abdominopelvic radiotherapy are a major problem for clinicians. These complications are treated with medications, antibiotics, anti-inflammatory drugs, hyperbaric oxygen, or by an interruption of therapy [4, 5]
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