Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Background: Ulcerative colitis (UC) is a disease related to a combination of genetic and environmental factors, associated with overproduction of both ROS and RNSleading to oxidative and nitrosative stress, as well as release of pro-inflammatory cytokines. Methods: The effect of sulfasalzine, pyrrolidine dithiocarbamate (PDTC) and saxagliptin was evaluated in thioacetamide (TAA)-induced UC model in the current study.Animals were treated orally with vehicle, sulfasalazine (500 mg/kg), PDTC (100 mg/kg), and saxagliptin (10 mg/kg) for two weeks,UC was induced by single intrarectal instillation of TAA at day eight. Colon samples were collected to assess colonic content of phosphorylated extraregular signal translated kinases (PERK), mitogen-activated protein kinase (MAPK), cAMP response element-binding protein (CREB), Interleukin (IL)-12, Caspase-3, Ý-defensin, glucagon like peptide (GLP)-1,inducible nitric oxide synthase (iNOS), as well as to perform histopathological investigations. Results:TAA-treated rats experienced increases in colon mass index, ulcerative area, colonic PERK, MAPK, CREB, caspase-3, IL-12,Ý-defensin, iNOS, together with decreases in body weight, colon mass index, ulcerative area and GLP-1 and distortion of colonic architecture, as shown by histopathological examination. PDTC and saxagliptin attenuated the severity of colitis, as demonstrated by decrease in body weight loss, colon mass index, ulcerative area as well as decrease in colonic PERK, MAPK, CREB, caspase-3, IL-12,Ý-defensin and iNOS

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