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Objective: To evaluate the antioxidant, immunomodulatory and anti-inflammatory activities of pyrrolidine dithiocarbamate and saxagliptin in rats with thioacetamide-induced ulcerative colitis. Methods: Animals were orally administered with a vehicle, sulfasalazine (500 mg/kg), pyrrolidine dithiocarbamate (100 mg/kg), and saxagliptin (10 mg/kg) for two weeks. Ulcerative colitis was induced by a single intrarectal instillation of thioacetamide on day 8. Colon samples were collected to assess mitogen-activated protein kinase (MAPK), phosphorylated extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), interleukin-12 (IL-12), caspase-3, β-defensin, inducible nitric oxide synthase (iNOS) and glucagon like peptide-1 (GLP-1). Moreover, histopathological examination was performed. Results: Rats treated with thioacetamide caused increases in colonic MAPK, phosphorylated ERK, CREB, caspase-3, IL-12, β-defensin, iNOS, as well as decreases in body weight and GLP-1. In addition, distortion of colonic structure was found by histopathological examination. Pyrrolidine dithiocarbamate and saxagliptin mitigated colitis severity by improving body weight decrease and GLP-1, and reducing colonic MAPK, phosphorylated ERK, CREB, caspase-3, IL-12, β-defensin and iNOS. Conclusions: Pyrrolidine dithiocarbamate and saxagliptin are efficient against thioacetamide induced colitis through improving inflammatory and oxidative changes. [ABSTRACT FROM AUTHOR]