Melatonin and roentgen irradiation-induced acute radiation enteritis in Albino rats: an animal model

Abstract

Background: Roentgen irradiation can affect normal cells, especially the rapidly growing ones such as the mucosal epithelial cells of the small intestine. The small intestine is the most radiosensitive gastrointestinal organ and patients receiving radiotherapy directed to the abdomen or pelvis may develop radiation enteritis. Although roentgen rays are widely used for both imaging and therapeutic purposes, our knowledge about the morphological changes associated with radiation enteritis is lacking.

Hypothesis: This study tries to tests the hypothesis that "the intake of melatonin can minimize the morphological features of cell damage associated with radiation enteritis".

Objectives and methods: We performed this investigation to test our hypothesis and to examine the possible radioprotective effects of melatonin in acute radiation enteritis. To achieve these goals, an animal model consisting of 60 Albino rats was established. The animals were divided into five groups: Group 1, non-irradiated; Group 2, X-ray irradiated (X-ray irradiation, 8 Grays); Group 3, X-ray irradiated-pretreated with solvent (ethanol and phosphate buffered saline); Group 4, non-irradiated-group treated with melatonin, and Group 5, X-ray irradiated-pretreated with melatonin. The small intestines were evaluated for gross (macroscopic), histological, morphometric (light microscopy), and ultrastructural changes (transmission electron microscopy).

Results: We found morphological variations among the non-irradiated-group, X-ray irradiated-group and X-ray irradiated-intestines of the animals pretreated with melatonin. The development of acute radiation enteritis in X-ray irradiated-group (Groups 2 and 3) was associated with symptoms of enteritis (diarrhea and abdominal distention) and histological features of mucosal injury (mucosal ulceration, necrosis of the epithelial cells). There was a significant reduction of the morphometric parameters (villous count, villous height, crypt height and villous/crypt height ratio). Moreover, the ultrastructural features of cell damage were evident including: apoptosis, lack of parallel arrangement of the microvilli, loss of the covering glycocalyx, desquamation of the microvilli, vacuolation of the apical parts of the cells, dilatation of the rough endoplasmic reticulum, and damage of the mitochondrial cristae. In the non-irradiated-group and in X-ray irradiated-intestines of the animals pretreated with melatonin (Group 5), these changes were absent and the intestinal mucosal structure was preserved.

Conclusion: Administration of melatonin prior to irradiation can protect the intestine against X-rays destructive effects, i.e. radiation enteritis. The clinical applications of these observations await further studies.