期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 765, 期 -, 页码 582-590出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2015.09.021
关键词
Crohn's disease; Inflammatory bowel diseases; Mixed opioid agonists; Visceral pain
资金
- Iuventus Plus program of the Polish Ministry of Science and Higher Education [0107/IP1/2013/72]
- Medical University of Lodz [503/1-156-04/503-01, 502-03/1-156-02/502-14-141]
- National Science Centre [UMO-2013/11/B/NZ7/01301, UMO-2014/13/B/NZ4/01179, UMO-2013/11/N/NZ7/00724, UMO-2014/12/T/NZ7/00252]
- NIDA [DA07315, DA023281]
- Polish L'Oreal UNESCO Awards for Women in Science
- Polpharma Scientific Foundation Scholarship
Endogenous opioid and nociceptin systems are widely distributed in the gastrointestinal tract where they seem to play a crucial role in maintaining the intestinal homeostasis. The aim of our study was to assess whether activation of nociceptin (NOP) and mu-opioid (MOP) receptors by a mixed NOP/MOP receptor agonist, BU08070, induces anti-inflammatory response in experimental colitis. The anti-inflammatory effect of BU08070 (1 mg/kg i.p.) was characterized in the mouse model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis, based on the assessment of the macroscopic and microscopic total damage scores and determination of myeloperoxidase (MPO) activity and TNF-alpha level in the colon. The effect of BU08070 on cell viability and NF-kappa B was characterized in THP-1 Blue cell line. The antinociceptive activity of BU08070 was examined in mustard oil-induced mouse model of abdominal pain. A potent anti-inflammatory effect of BU08070 (1 mg/kg i.p.) was observed as indicated by decrease in macroscopic damage score (1.88 +/- 0.39 vs. 5.19 +/- 0.43 units in TNBS alone treated mice), MPO activity (2.29 +/- 0.37 vs. 9.64 +/- 2.55 units) and TNF-alpha level in the colon (35.85 +/- 2.45 vs. 49.79 +/- 3.81 pg/ml). The anti-inflammatory effect of BU08070 was reversed by selective NOP and MOP receptor antagonists. BU08070 produced concentration-dependent inhibition of TNF-alpha and LPS-induced NF-kappa B activation. BU08070 exerted antinociceptive action in mice with experimental colitis. In conclusion, BU08070 significantly reduced the severity of colitis in TNBS-treated mice compared with controls. These results suggest that BU08070 is a potential therapeutic agent for inflammatory bowel diseases therapy. (C) 2015 Elsevier B.V. All rights reserved.
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