Alterations to digestive motricity combined with inflammatory processes induced by ionizing radiation .
Doctorate thesis of the University of Paris VII Denis Diderot
defended on the 18th December 2000
Exposure to ionising radiation, whether accidental or for medical reasons, may lead to gastro-intestinal injury, characterised by nausea, vomiting, diarrhoea and abdominal cramps. The aetiology of radiation induced-diarrhoea remains to date unclear. In this study, we have investigated the acute effects of a 10 Gy abdominal irradiation on rat digestive functions. The objective of the first study was to evaluate the role of sensory afferent neurons, capsaicin-sensitive, on morphological changes and the inflammatory response following exposure. Three days after irradiation, we observed an inflammatory response characterised by neurtrophils infiltration and mast cells degranulation; no effect of capsaicin pre-treatment was seen on these parameters. However, neutrophils infiltration was increased as early as one day after irradiation in capsaicin-treated rats. No difference in severity of diarrhoea was observed after denervation nor in morphological changes. These data demonstrate that abdominal irradiation results in dirrhoea concomitant with an inflammatory response, and that sensory innervation does not play a major protective role. The objective of the rest of the work was in the first instance to characterise radiation induced-alterations of intestinal and colonic motility leading to diarrhoea and secondly to evaluate the role of serotonin in such disorders. Perturbations in intestinal (MMC) and colonic (LSB) motor profiles were observed from the first day onwards. Migrating Motor Complexes were completly disrupted at three days at the same time as the decreased and serotonin colonic tissue levels were increased three days after irradiation. Radiation induced-diarrhoea was reduced bt treatment with an antagonist of 5-HT3 receptors, granisetron, as were alterations of colonic motility and serotonin tissue levels. However, this treatment, did not significantly ameliorate fluid absorption on three days. These two studies show that a 10 Gy abdominal irradiation markedly affects intestinal and colonic motility both of which contribute to the ensuing diarrhoea, and a role for serotonin via 5-HT3 receptors. In conclusion, these results demonstrate functional modifications without marked alterations of intestinal and colonic morphology. These changes are concomitant with an inflammatory response which does not appear to involve afferent nerves. However, serotonin plays an important role in the inhibition of colonic motility and in consequence in the establishment of diarrhoea.