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Abstract:
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Diarrhea is a common symptom of individuals undergoing radiation therapy for abdominopelvic malignancies suggesting that absorptive and secretory processes of the gut may be altered. Studies indicate that radiation stimulates an acute inflammatory response, releasing inflammatory mediators which may stimulate the induction of nitric oxide synthase. To determine the role of nitric oxide in the radiation-induced alterations in electrolyte transport we measured changes in nitric oxide synthase activity in the jejunum, ileum and colon of rats at various times after whole body irradiation (10 Gray) and after sham treatment. To further determine the importance of nitric oxide in the gut, rats were treated with the competitive nitric oxide synthase inhibitor, nitro-L-arginine methylester one hour prior to irradiation or sham treatment and the above procedures repeated. Radiation decrease the short circuit current response to neurally-evoked stimulation in the jejunum, ileum and colon in a time-dependent fashion. The radiation-induced alterations in electrolyte transport did not coincide with changes in nitric oxide synthase activity. Radiation transiently decreased nitric oxide synthase activity in the jelunum at 0.5h post-irradiation. In the ileum, radiation increased nitric oxide synthase activity from 2-24h post-irradiation. Thus, alterations in intestinal electrolyte transport occurred in the absence of a major inflammatory response and without damage to the epithelium. The results demonstrate that radiation can cause alterations in electrolyte transport in the rat intestine in the absence of an acute inflammatory response or significant changes in epithelial morphology. Radiation can stimulate inducible nitric oxide synthase activity in the rat ileum. The increase in nitric oxide production is likely a protective mechanism rather than damaging to epithelial function. |
