الفهرس 
Review of literature
Methods of Induction of Experimental UCOnly 14 pages are availabe for public view
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Abstract
Ulcerative colitis (UC) is considered a public health problem worldwide. In 2015, 1.3% of United States adults (3 million) reported being diagnosed with IBD (either chron’s disease or ulcerative colitis. This was considered a large increase from 1999 (0.9% or 2 million adults). While prevalence of UC in the Middle East and Africa still lower than in united states and Europe, it appear to be increasing in the past few years. In Egypt, recent studies reported increasing incidence of UC in the past five years.
The etiologic and pathogenic mechanism of UC is still not completely understood, some experimental and clinical studies indicate that its pathogenesis is mainly associated with oxidative stress, apoptosis and inflammatory response.
DSS induced UC model is considered a well-standardized model to study the beneficial effects of many drugs. It produces dysfunction in the mucosal defense mechanism and increases production of ROS.
2-mercaptoethane sodium sulphonate (Mesna) is a chemotherapy adjuvant with well-known anti-oxidative, anti-inflammatory and anti-apoptotic properties.
Sulfasalazine is a drug with well-known therapeutic effect in UC. It consists of 5-ASA linked to a sulfa moiety by a di-azo bond. The mechanisms involved in its therapeutic effects are not completely understood; it has anti-inflammatory, immunosuppressive, and bacteriostatic actions.
The aim of the present work was to find novel treatments for DSS–induced UC in a rat model, the effect of treatment with Mesna and /or sulfasalazine on rats with DSS–induced UC was examined, using several physiological, biochemical, immunological and histopathological methods, with a special focus on the possible effects of Mesna and/or sulfasalazine on the anti-inflammatory and antioxidant mechanisms in DSS – induced UC.
Experimental design:
Forty adult male Sprague Dawly albino rats were used in this study and were divided randomly into 5 groups each group consist of 8 rats as follow:
Control group: they were used as control for all groups.
DSS group (UC group): Received 5% dextran sulfate sodium (MW 36,000–50,000) to drinking water for 7 days.
DSS+ Mesna group: Received dextran sulfate sodium 5% in drinking water for 7 days followed by Mesna intra-peritoneal by a dose of (400mg/kg/day) for further 10 days.
DSS+ sulfasalazine group: Received dextran sulfate sodium 5% in drinking water for 7 days followed by sulfasalazine oral by a dose of (300mg/kg/day) for further 10 days.
AD+ combination group: Rats were received dextran sulfate sodium 5% in drinking water for 7 days followed by Mesna intra-peritoneal by a dose of (400mg/kg/day) and sulfasalazine oral by a dose of (300mg/kg/day) for further 10 days.
Summary
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During the time course of the experiment, Rats body weight was measured every other day, rats were observed during the experimental period regarding stool consistency and rectal bleeding. At the end of the experiment, animals were decapitated and colons were excised. Colon length of each rat was measured; gross pathological changes were observed and recorded. Each colon was divided into two halves. One half used for measurement of tissue level of GSH and SOD. The other half of colonic was stained by Hx&E for assessment of histopathological changes and immunohistochemical (IHC) staining for tumor necrosis factor- α (TNF-α).
In the present study, administration of DSS produced UC with a significant decrease in final body weight, significant increase in DAI, significant decrease in oxidative stress biomarkers GSH and SOD when compared to control group. By gross pathological examination, there were significant decrease in the colon length, hyperemia, edema and ulceration. By histopathological examination there was significant damage in colon tissue by H&E. In addition, DSS treated group showed marked increase in the intensity of TNF-α IHC staining and significantly increase in TNF-α H-score compared to control group.
Treatment of DSS group with Mesna, sulfasalazine or their combination significantly decreased body weight loss, DAI, and significantly increased tissue level of GSH and SOD compared to DSS group.
Regarding gross and histopathological examination, treatment of DSS group with Mesna, sulfasalazine or their combination produced marked improvement in gross and histopathological parameters and significant decrease in the intensity of TNF-α IHC staining and TNF-α H-score compared to DSS group.