Medizinische Universität Graz - Research portal
Selected Publication:
Schmidt, L.
Therapeutic potential of gut stable oxytocin analogues in DSS-colitis.
[ Diplomarbeit/Master Thesis (UNI) ] Universität Graz; 2023.
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- Authors Med Uni Graz:
- Advisor:
- Farzi Aitak
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- Abstract:
- Background: Inflammatory bowel diseases (IBD) are a chronic, inflammatory condition of the gastrointestinal tract. They include the two most common clinical conditions, Crohn's disease and ulcerative colitis. The exact etiology is unknown and the global rise of IBD cases, particularly in developed countries, emphasizes the importance of research in this area. To address this need, different animal models have been established for research purposes. Oxytocin (OT) has numerous other functions besides its roles in childbirth and lactation, including potential anti-inflammatory effects and dampening of DSS-induced colitis. The aim of this work was to investigate the effects of a novel gut-stable OT analogue as a potential therapeutic drug in a mouse model of chemical-induced colitis, which in contrast to OT does not get degraded in the gastrointestinal tract.Methods: Acute colitis was induced in male C57BL/6J mice by administration of 2% DSS for a period of seven days. OT treatment started two days before DSS-administration and continued until the last day of the experiment (day 0-10). Two different administration routes were investigated (i) oral administration at a concentration of 1 mg/kg and (ii) intraperitoneal (i.p.). administration at 0.1 mg/kg. In addition to endogenous OT, a gut-stable OT (OTgs) analogue was tested. The progression of colitis was studied using various parameters, including the degree of inflammation with the disease activity score as well as gene expression of pro-inflammatory cytokines and microscopic analysis of intestinal tissue, water and food consumption, as well as locomotor and anxiety behavior using the open field test. Results: DSS-induced colitis in mice resulted in weight loss, increased inflammatory response with increased cytokines levels and inflammatory cells infiltrating the colonic mucosa, but also increased anxiety-like behavior and locomotor impairment. Oral administration of 1 mg/kg OT or OTgs was unable to alleviate these symptoms. By contrast, the i.p.-injected OT at a concentration of 100 µg/kg delayed the onset of colitis symptoms, including weight loss and showed protection against intestinal damage. In contrast no beneficial effects of OTgs on weight loss, the histological score, and the locomotor activity could be observed. Conclusion: OT exhibits a potential therapeutic effect on colitis disease patterns in mice when administered i.p. at 100 µg/kg. The ineffectiveness of the oral administration may be due to low concentration reaching the colon. Therefore, higher oral concentrations should be investigated in the future. The reason for the negative effect of the OTgs could not be clarified in the present work, and further research is needed to provide more insights into its mode of action.