The effect of indomethacin on acute radiation induced gastrointestinal injury: A morphologic study

Abstract

Radiation-induced intestinal injury is a dose limiting factor in the treatment of pelvic, abdominal, and retroperitoneal malignancies with radiation therapy. In experimental models, radiation has been associated with increased intestinal prostaglandin activity and in clinical trials prostaglandin inhibitors have been demonstrated to improve the symptoms of acute radiation enteritis. This study was conducted to determine if the prostaglandin inhibitor indomethacin could prevent the morphologic changes of acute radiation induced intestinal injury. Twenty-four male rats received either parenteral indomethacin at doses of 0.5, 1.0, and 3.0 mg/kg per dose every 12 hours or saline from 24 hours pre-radiation exposure until sacrifice 48 hours later. Twenty-four control animals received identical drug dosages and anesthesia but no radiation. Radiation produced a decreased villus/crypt ratio and increased acute inflammation and degeneration. Indomethacin treated animals demonstrated significantly less polymorphonuclear leukocyte infiltration and decreased degeneration. Villus/crypt ratio was not affected by indomethacin.

Increased Expression of Cyclooxygenase-2 (COX-2) in Radiation-Induced Small Bowel Injury in Rats

“…In experimental models, radiation has been associated with an increase in intestinal prostaglandin activity, and in clinical trials, prostaglandin inhibitors have been shown to improve the symptoms of acute radiation enteritis [14]. This study was conducted to evaluate COX-2 expression in acute and late stages of radiation-induced intestinal injury, and to investigate the possible protective effect of the selective COX-2 inhibitor, Rofecoxib, against radiation-induced intestinal injury in rats.…”

Pulp Vitality in Patients with Intraoral and Oropharyngeal Malignant Tumors Undergoing Radiation Therapy Assessed by Pulse Oximetry

“…Inflammatory responses after irradiation have been shown in other tissues and organs. Interstitial inflammation involving polymorphonuclear leukocytes was observed by histological examination of irradiated intestinal tissues (20,21). Pneumonitis was observed 2 to 6 months after lung irradiation with doses of 8 Gy (22).…”

Amelioration of the pathological changes induced by radiotherapy in normal tissues

“…However, administration of sodium salicylate and indometacin together decreased the beneficial effects of indometacin. Rose et al (1992) reported reduced polymorphonuclear leucocyte infiltration and decreased tissue degeneration in indometacintreated rats after 50 Gy (single dose) of whole-abdomen irradiation.…”