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

• DOI: 10.1038/srep39863
• Publication Date: 2017-01-09T10:06:10Z
• Authors: Ádám Horváth; Awt Menghis; Bálint Botz; Éva Borbély; Ágnes Kemény; Valéria Tékus; Janka Zsófia Csep...; Attila Mócsai; Tamás Juhász; Róza Zákány; Dóra Bogdán; Péter Mátyus; Julie Keeble; Erika Pintér; Zsuzsanna Helyes
• Keywords: Freund's Adjuvant; Anti-Inflammatory Agents; 610; Mice, Inbred Strains; Mice, Transgenic; Article; Mice; 03 medical and health sciences; Oximes; Animals; Humans; Elméleti orvostudományok; Oxazoles; Cells, Cultured; 0303 health sciences; RZ Other systems of medicine / orvostudomány egyéb területei; Arthritis; Orvostudományok; Analgesics, Non-Narcotic; Disease Models, Animal; Hydrazines; Chronic Disease; Disease Progression; R850-854 Experimental medicine / kisérleti orvostudomány; Joints; Amine Oxidase (Copper-Containing)

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 our novel SSAO inhibitor SzV-1287 chronic mouse models joint inflammation. Effects (20 mg/kg i.p./day) were K/BxN serum-transfer complete Freund’s adjuvant (CFA)-evoked active immunization compared to reference LJP-1207. Mechanonociception was assessed by aesthesiometry, oedema plethysmometry, clinical severity scoring, grid test, myeloperoxidase activity luminescence, vascular leakage fluorescence vivo imaging, histopathological changes semiquantitative evaluation, cytokines Luminex assay. significantly inhibited hyperalgesia both models. Plasma keratinocyte chemoattractant production tibiotarsal joint, but not reduced K/BxN-arthritis. did influence cellular mechanisms CFA-arthritis, decreased alterations. There difference anti-hyperalgesic anti-inflammatory actions LJP-1207, only CFA-induced tissue damage. Unlike SzV-1287, LJP-1207 induced cartilage destruction, which confirmed vitro . exerts potent analgesic distinct without inducing