Histomorphologic Changes of Small Intestinal Mucosa after Irradiation in Rats

Kim, Chan Hwan; Chang, Eun Sook; Kwon, Keon Young; Park, Kwan Kyu; Kim, Ok Bae

Abstract

Inadvertent application of ionizing radiation, a valuable tool in diagnostic radiology and radiotherapy, results in injury and death of adjacent normal cells, inducing gene mutations or even producing latent cancers. Captopril, an angiotensin I converting enzyme (ACE) inhibitor, has been reported to prevent the structural and functional changes in variable organs, such as lung and kidney, from radiation injury in different experimental animal models. An experiment was carried out to elucidate the radiation-induced histomorphologic changes of small intestine, especially jejunum, and to determine whether captopril can reduce or prevent the radiation-induced injuries in jejunum. Twenty-six healthy Sprague-Dawley rats were used. Experimental group (n=24) was divided into two large groups: the first one (n=16) was treated with two different single dose (9 Gy, 17 Gy) irradiation only and was sacrificed at 12 hours and at 8 weeks following irradiation; the second one (n=8) received captopril 500 mg/l per oral continuously after same doses of irradiation and was sacrificed at 8 weeks. The control group (n=2) was maintained on a stock diet in a same period of experimental group and sacrificed coincidentally. On light and electron microscopy, the 9 Gy and 17 Gy 12 hours groups revealed frequent apoptosis and necrosis but extremely decreased mitotic figures of the crypt cells. However, the 9 Gy and 17 Gy 8 weeks groups and the combined irradiation with captopril groups showed extremely reduced apoptosis and necrosis with increased mitotic figures. There was good correlation between experimental groups in apoptotic count and mitotic count (p<0.05). In the 9 Gy and 17 Gy 12 hours groups, the mucosal surface was focally or diffusely fragmented and the villi were slightly to moderately distorted. Collagen deposition was very mild and confined to the lower portion of the lamina propria. The 9 Gy and 17 Gy 8 weeks groups showed more severe mucosal surface fragmentation even with foci of erosion, short and distorted villi, and more intense collagen deposition. In contrast, the combined irradiation with captopril groups revealed complete regeneration of the mucosal surface epithelium and absent collagen deposition. These findings suggest that the acute radiation injuries to small intestine occur principally in the mucosal crypt cells. Captopril, the ACE inhibitor, might provide a useful intervention in the radiation injuries of intestinal mucosa.