PREVENTION OF CHRONIC RADIATION ENTEROPATHY BY DIETARY GLUTAMINE

Background: Nearly 50% of all cancer patients receive therapeutic radi ation during the course of their disease. The risk of late complicatio ns is the main dose-limiting factor in the delivery of radiation thera py. The small intestine, the major site of chronic radiation enteropat hy, is also the principal organ of glutamine consumption. We therefore hypothesized that the provision of supplemental glutamine may have a protective effect on the development of chronic radiation enteropathy. Methods: This study evaluated the effects of supplemental oral glutam ine on the development of chronic radiation (XRT) enteropathy. After s crotalization of a loop of small intestine, rats were randomized to re ceive 1 g/kg/day glutamine (GLN) or glycine (GLY) by gavage. After 2 d ays of prefeeding, rats were randomized to 1 of 4 groups: GLN + XRT (n = 10), GLY + XRT (n = 10), GLN only (n = 10), GLY only (n = 10). Twen ty Gy was delivered to the scrotalized bowel in the GLN + XRT and GLY + XRT groups via a collimated beam. Gavage was continued for 10 days. Animals were then pair-fed chow. Rats were killed at 2 months postirra diation. Chronic radiation injury was assessed microscopically. Result s: Injury scores in GLN + XRT were similar to those of unirradiated bo wel and significantly different from GLY + XRT (1.89 +/- 0.48 in XRT GLN vs. 6.42 +/- 1.55 in the XRT + GLY, p < 0.01). Elevated Injury Sc ores in the XRT + GLY group correlated with gross thickening and fibro sis, a 10-fold decrease in gut GLN extraction (1.40 +/- 4.3% in GLY XRT vs. 16.0 +/- 5.1% in GLN + XRT, p < 0.05), and a 30% decrease in g lutathione content (2.46 +/- 0.19 and GLY + XRT vs. 3.17 +/- 0.17 GLN + XRT, p < 0.05). Conclusions: Provision of GLN during abdominal/pelvi c XRT may prevent XRT injury and decrease the long-term complications of radiation enteropathy.