| Abstrakt: |
Introduction and aim. There is no safe and efficient treatment of the chronic intestinal inflammation. Kappa Opioid Receptors (KOP) are found not only in the central nervous system, but also in the gastrointestinal tract. Studies showed that KOP agonist can reduce inflammation in numerous experimental inflammatory models. The aim of the study was to assess if activation of KOP will give anti-inflammatory action in the experimental model of colitis. Material and methods. Dextran Sulfate Sodium was given to mice for 7 days, following 14 days of water, this cycle was repeated twice. We used a selective KOP agonist, U50488, at the dose of 1mg/kg injected intraperitoneally every second day. Following morphological grading, colonic tissues were isolated for molecular analysis. In vitro tests were performed using the RAW 264.7 macrophage cell line, and lipopolysaccharide (LPS) was used to mimic inflammation. The Griess test and MTT assay were used to evaluated how U50488 affects the cytotoxicity and viability of the cells. Results. Anti-inflammatory properties of U50488 were observed by overall improvement in macroscopic scoring, and improvement in microscopic scoring. Moreover, RT-PCR results show changes in NOS2, IL-1B and Il-6 expression, that indicate anti-inflammatory potential of KOP agonist. Results obtained in vitro confirmed that U50488 affected cell survival and decreased NO release, indicating that it has anti-in- flammatory effects. Conclusion. Activation of KOP with U50488 may become novel approach in treatment of chronic colitis. [ABSTRACT FROM AUTHOR] |
