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

Ádám Horváth, Awt Menghis, Bálint Botz, Éva Borbély, Ágnes Kemény, Valéria Tékus, Janka Zsófia Csepregi, Attila Mócsai, Tamás Juhász, Róza Zákány, Dóra Bogdán, Péter Mátyus, Julie Keeble, E. Pintér, Zsuzsanna Helyes

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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.

Original languageEnglish
Article number39863
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - Jan 9 2017

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Amine Oxidase (Copper-Containing)
Freund's Adjuvant
Non-Steroidal Anti-Inflammatory Agents
Arthritis
Joints
Peroxidase
Cartilage
Blood Vessels
Edema
Deamination
Experimental Arthritis
Hyperalgesia
Chemotactic Factors
Luminescence
Keratinocytes
Amines
Vaccination
Anti-Inflammatory Agents
Fluorescence
Cytokines

ASJC Scopus subject areas

  • General

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Analgesic and Anti-Inflammatory Effects of the Novel Semicarbazide-Sensitive Amine-Oxidase Inhibitor SzV-1287 in Chronic Arthritis Models of the Mouse. / Horváth, Ádám; Menghis, Awt; Botz, Bálint; Borbély, Éva; Kemény, Ágnes; Tékus, Valéria; Csepregi, Janka Zsófia; Mócsai, Attila; Juhász, Tamás; Zákány, Róza; Bogdán, Dóra; Mátyus, Péter; Keeble, Julie; Pintér, E.; Helyes, Zsuzsanna.

In: Scientific Reports, Vol. 7, 39863, 09.01.2017.

Research output: Contribution to journalArticle

Horváth, Á, Menghis, A, Botz, B, Borbély, É, Kemény, Á, Tékus, V, Csepregi, JZ, Mócsai, A, Juhász, T, Zákány, R, Bogdán, D, Mátyus, P, Keeble, J, Pintér, E & Helyes, Z 2017, 'Analgesic and Anti-Inflammatory Effects of the Novel Semicarbazide-Sensitive Amine-Oxidase Inhibitor SzV-1287 in Chronic Arthritis Models of the Mouse', Scientific Reports, vol. 7, 39863. https://doi.org/10.1038/srep39863
Horváth, Ádám ; Menghis, Awt ; Botz, Bálint ; Borbély, Éva ; Kemény, Ágnes ; Tékus, Valéria ; Csepregi, Janka Zsófia ; Mócsai, Attila ; Juhász, Tamás ; Zákány, Róza ; Bogdán, Dóra ; Mátyus, Péter ; Keeble, Julie ; Pintér, E. ; Helyes, Zsuzsanna. / Analgesic and Anti-Inflammatory Effects of the Novel Semicarbazide-Sensitive Amine-Oxidase Inhibitor SzV-1287 in Chronic Arthritis Models of the Mouse. In: Scientific Reports. 2017 ; Vol. 7.
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