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ORIGINAL ARTICLE
Year : 2019  |  Volume : 9  |  Issue : 9  |  Page : 373-380

Pyrrolidine dithiocarbamate and saxagliptin ameliorate ulcerative colitis in rats


1 Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
2 Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Egypt

Correspondence Address:
Berween Mahmoud Elmahmoudy
Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2221-1691.267638

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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.


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