الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Ulcerative colitis (UC) is a subtype of inflammatory bowel disease and is characterized by an intermittent episode of relapse, followed by remission and finally resulting in mucosal damage. In this study, the protective effect of NO donor molsidomine, and the dual COX / LOX inhibitor flavocoxid that work on different pathways involved in AA-induced UC was investigated. Rats were pretreated with flavocoxid (10 and 20 mg/kg, O.P.) and molsidomine (1 and 2 mg/kg, I.P) 7 days prior to intra-rectal instillation of AA (2 ml of 4% AA in normal saline) then blood samples were collected from retro-orbital sinus, centrifuged for 15 min at 3000 rpm and the sera were obtained for determination of liver enzymes (ALT and AST). Colon and liver tissues were collected after sacrification to determine disease activity index, colon mass index, colonic macroscopic damage, histopathological changes and biomarkers of oxidative stress. In addition, TNF-α, NF-κB/p65, MPO and iNOS were assessed in colonic and hepatic homogenates using ELISA technique. Moreover, Caspase 3 and Bax expression was assessed in colonic and hepatic tissues using immunohistochemistry technique. AA-induced UC is elucidated by increasing disease activity index, colon mass index, colonic macroscopic damage and MDA content as well as decreasing GSH level and SOD activity in colonic and hepatic homogenates. Moreover, AA increased levels of TNF-α, NF-κB/p65, MPO and iNOS in colonic and heptic homogenates. Additionally, AA upregulated caspase-3 and Bax expression in colonic and hepatic tissues. Pretreatment with either flavocoxid or molsidomine protected against AA-induced UC by decreasing disease activity index, colon mass index, colonic macroscopic damage, MDA, NOx and restoring the decreased GSH level and SOD activity. Additionally, both drugs managed to decrease TNF-α, NF-κB/p65, MPO and iNOS levels in colonic and hepatic homogenates and down-regulated caspase 3 and Bax expression and hence apoptosis. Conclusion: Flavocoxid and molsidomine halted both intestinal and extra-intestinal alterations in experimental colitis model induced by AA. This effect, was more obvious in the higher dose of flavocoxid (20 mg/kg) and molsidomine (2 mg/kg), might be due to their ability to reduce inflammation, oxidative stress, and apoptosis in both colonic and hepatic tissues. Further investigations are required to assure the use of flavocoxid and molsidomine in the treatment of human UC.