Analgesic and Anti-Inflammatory Effects of the Novel Semicarbazide-Sensitive Amine-Oxidase Inhibitor SzV-1287 in Chronic Arthritis Models of the Mouse

Sci Rep. 2017 Jan 9;7:39863. doi: 10.1038/srep39863.

Abstract

Semicarbazide-sensitive amine oxidase (SSAO) catalyses oxidative deamination of primary amines. Since there is no data about its function in pain and arthritis mechanisms, we investigated the effects of our novel SSAO inhibitor SzV-1287 in chronic mouse models of joint inflammation. Effects of SzV-1287 (20 mg/kg i.p./day) were investigated in the K/BxN serum-transfer and complete Freund's adjuvant (CFA)-evoked active immunization models compared to the reference SSAO inhibitor LJP-1207. Mechanonociception was assessed by aesthesiometry, oedema by plethysmometry, clinical severity by scoring, joint function by grid test, myeloperoxidase activity by luminescence, vascular leakage by fluorescence in vivo imaging, histopathological changes by semiquantitative evaluation, and cytokines by Luminex assay. SzV-1287 significantly inhibited hyperalgesia and oedema in both models. Plasma leakage and keratinocyte chemoattractant production in the tibiotarsal joint, but not myeloperoxidase activity was significantly reduced by SzV-1287 in K/BxN-arthritis. SzV-1287 did not influence vascular and cellular mechanisms in CFA-arthritis, but significantly decreased histopathological alterations. There was no difference in the anti-hyperalgesic and anti-inflammatory actions of SzV-1287 and LJP-1207, but only SzV-1287 decreased CFA-induced tissue damage. Unlike SzV-1287, LJP-1207 induced cartilage destruction, which was confirmed in vitro. SzV-1287 exerts potent analgesic and anti-inflammatory actions in chronic arthritis models of distinct mechanisms, without inducing cartilage damage.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amine Oxidase (Copper-Containing) / antagonists & inhibitors*
  • Analgesics, Non-Narcotic / therapeutic use*
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Arthritis / drug therapy*
  • Cells, Cultured
  • Chronic Disease
  • Disease Models, Animal
  • Disease Progression
  • Freund's Adjuvant / immunology
  • Humans
  • Hydrazines / pharmacology
  • Hydrazines / therapeutic use*
  • Joints / drug effects
  • Joints / pathology*
  • Mice
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Oxazoles / pharmacology
  • Oxazoles / therapeutic use*
  • Oximes / pharmacology
  • Oximes / therapeutic use*

Substances

  • 3-(4,5-diphenyl-1,3-oxazol-2-yl)propanal oxime
  • Analgesics, Non-Narcotic
  • Anti-Inflammatory Agents
  • Hydrazines
  • N'-(2-phenylallyl)hydrazine
  • Oxazoles
  • Oximes
  • Freund's Adjuvant
  • Amine Oxidase (Copper-Containing)