thromboplastin and Intestinal-Diseases

The small bowel is a dose-limiting normal tissue in radiation therapy of malignancies in the abdomen and pelvis, as well as an important determinant of survival after non-therapeutic radiation exposure. Irradiation of normal tissues, including intestine, causes loss of vascular thromboresistance and upregulation of thrombin receptors. Radiation-induced endothelial dysfunction is thought to be involved in both early and delayed radiation responses. Hence, thrombin may be a potential target for ameliorating normal tissue radiation toxicity.. To assess direct thrombin inhibition as a protective strategy against small bowel radiation toxicity.. Rat small intestine was exposed to localized orthovoltage X-radiation. Recombinant hirudin, a direct thrombin inhibitor, or vehicle was infused from 2 days before irradiation to 14 days after irradiation. Structural, cellular, and molecular aspects of intestinal radiation injury were assessed at 2 weeks (early toxicity) and 26 weeks (chronic toxicity) after irradiation.. Compared with unirradiated intestine, irradiated intestine showed increased expression of tissue factor, increased immunoreactivity for enzymatically active thrombin, and increased extravascular fibrin(ogen) deposition. Hirudin treatment significantly attenuated radiation-induced mucosal damage (P = 0.04), reactive intestinal wall thickening (P = 0.02), transforming growth factor-beta immunoreactivity levels (P = 0.0002), and collagen III deposition (P = 0.003). The differences between hirudin-treated and control rats were more pronounced at 2 weeks than at 26 weeks after irradiation. Hirudin treatment did not affect postradiation granulocyte infiltration.. Short-term thrombin inhibition attenuates important aspects of intestinal radiation toxicity. Thrombin is a promising target for minimizing normal tissue injury after radiation therapy of cancer, as well as for protecting normal tissues from the adverse effects of non-therapeutic radiation exposure.

Topics: Animals; Fibrin; Gamma Rays; Hirudins; Intestinal Diseases; Intestines; Male; Radiation Injuries; Radiation Tolerance; Radiation-Protective Agents; Rats; Rats, Sprague-Dawley; RNA, Messenger; Thrombin; Thromboplastin