Anti-inflammatory effect of dual nociceptin and opioid receptor agonist, BU08070, in experimental colitis in mice

Marta Zielińska, Tanila Ben Haddou, Gerta Cami-Kobeci, Maciej Sałaga, Agata Jarmuż, Milena Padysz, Radzisław Kordek, Mariana Spetea, Stephen M Husbands, Jakub Fichna

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

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 µ-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-α level in the colon. The effect of BU08070 on cell viability and NF-κB 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-α 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-α and LPS-induced NF-κB 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.

Original languageEnglish
Pages (from-to)582-90
Number of pages9
JournalEuropean Journal of Pharmacology
Volume765
DOIs
Publication statusPublished - 15 Oct 2015

Keywords

  • Animals
  • Anti-Inflammatory Agents/pharmacology
  • Buprenorphine/analogs & derivatives
  • Cell Line
  • Colitis/chemically induced
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Opioid/agonists
  • Treatment Outcome
  • Trinitrobenzenesulfonic Acid/toxicity

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