Expression, activity and cellular localization of inducible nitric oxide synthase in rat ileum and colon post-irradiation

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Abstract
Purpose: Studies were conducted to determine the acute effect of exposure to ionizing radiation on inducible nitric oxide synthase (iNOS) activity and expression in the rat ileum and colon. Materials and Methods: Rats received whole body exposure to 10 Gy gamma -radiation and were studied 0 5-48 h later. Segments of ileum and colon were taken from anaesthetized rats for determination of myeloperoxidase activity (a marker of acute inflammation), and iNOS mRNA expression, enzyme activity and localization. Results: Myeloperoxidase activity in ileum was not increased compared with shams until 48 h post-irradiation. In colon, myeloperoxidase activity was lower than shams at 48 h postirradiation. Irradiation resulted in a dexamethasone-sensitive expression of iNOS mRNA in both the ileum and colon within 2 h. Inducible NOS activity was significantly elevated in the ileum, but not in the colon. The elevated ileal nitric oxide synthase activity was significantly reduced by pretreatment with the iNOS inhibitor, aminoguanidine. Immunoreactivity for iNOS protein was localized to the epithelium and was apparent at 2-6 h post-irradiation in the ileum, but not the colon. Conclusions: Exposure to ionizing radiation results in the expression of iNOS in ileum and colon, but only significantly increases iNOS activity in the ileum. Inducible NOS-derived NO may participate in acute, whole body radiation-induced ileal dysfunction, independently of the development of an inflammatory response.