Inhibition of protease-activated receptor 1 ameliorates intestinal radiation mucositis in a preclinical rat model.
RatRadiationSprague-Dawleymalen = 120 male rats in total: 30 in the early toxicity experiment…Subcutaneous, dissolved in 0.4% methylcelluloseEarly toxicity arm 10 or 15 per kg per day; delayed fibrosi…Started 1 day before the first radiation fraction
Model: Localised fractionated X-irradiation (5 Gy on each of 9 days, 250 kVp, dose rate 4.49 Gy/min) of a 4 cm loop of distal ileum transposed into the scrotum, producing early radiation mucositis and delayed radiation fibrosis
At 2 weeks PAR1 blockade reduced the radiation injury score (p=0.002), myeloperoxidase-positive cells (p=0.03), smooth muscle cell proliferation (p=0.04) and collagen III immunoreactivity (p=0.005) in a dose dependent manner, but neither short-term nor long-term administration altered delayed intes…
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