Study on SSAO enzyme activity and anti-inflammatory effect of SSAO inhibitors in animal model of inflammation

Abstract

SSAO/VAP-1 participates in the accumulation of leukocytes at the site of inflammation. A new SSAO inhibitor, SzV-1287 was demonstrated to inhibit both acute and chronic inflammation in rats more effectively than the known enzyme inhibitor, LJP-1207. Surprisingly, the SSAO activity was not increased, but decreased both in acute and chronic inflammation. Though experiments are in progress to clarify these findings, the enzyme might play a role in the very early phase of inflammation and be inactivated during leukocyte extravasation.

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

“…Although we are the first to report the analgesic actions of SSAO inhibition, the described anti-inflammatory effects are in agreement with previous data showing anti-oedema effects for SzV-1287 in carrageenan- and CFA-induced paw inflammation models in the rat25. However, the most remarkable difference between the effects of the two compounds was the significant reduction in the inflammatory histopathological alterations (mononuclear cell infiltration and cartilage damage) in SzV-1287-treated mice, while chronic LJP-1207 treatment actually worsened the cartilage destruction at the 20 mg/kg i.p.…”

“…Although LJP-1207 showed greater potency in the inhibition of human SSAO activity in an in vitro enzyme assay compared to SzV-1287 (IC 50 : 1.7 × 10 −8  M and IC 50 : 3.5 × 10 −6  M, respectively)25, there was no significant difference between their actions in our chronic in vivo experiments. The described anti-inflammatory effects are novel in relation to arthritis, but they are explained by the already known vascular and cellular mechanisms of SSAO inhibition and supported by previous literature11161718.…”

“…The cartilage damaging action of LJP-1207 in the chronically inflamed joint is not likely to be due to its SSAO inhibitory effect, since a very recently published paper reports that SSAO inhibition delayed the chondrocyte differentiation without any alteration of cell viability in vitro 38; this might be related to some other mechanisms due to its different structure. The unique features of SzV-1287 compared to other SSAO inhibitors are its COX inhibitory action, without ulcerogenic effects25, and potent dual antagonistic property at the TRPV1/TRPA1 ion channels localised on peptidergic sensory nerves39, inflammatory cells40, and chondrocytes4142. The importance of TRPV1/TRPA1-dependent neurogenic inflammatory mechanisms in RA has been extensively investigated and received a great attention434445.…”

“…One of the first publications on the effects of this compound reported its anti-inflammatory action in carrageenan-induced acute and adjuvant-induced chronic inflammation models of the rat25. We have recently shown that SzV-1287 is also able to antagonise Transient Receptor Potential Vanilloid 1 and Ankyrin 1 (TRPV1 and TRPA1) receptors expressed on nociceptive primary sensory neurons involved in inflammation and pain.…”

Fabrication of endothelial progenitor cell capture surface via DNA aptamer modifying dopamine/polyethyleneimine copolymer film

“…A multifunctional enzyme named semicarbazide-sensitive amine oxidase (SSAO) could convert primary amines into their corresponding aldehydes, while generating H 2 O 2 and NH 3 , and it wildly presented in nature [50,51]. In mammals, SSAO circulates in plasma, while a membrane-bound form is found in many tissues and organs, especially in adipocytes and vascular endothelial and smooth muscle cells [52]. Hence, primary amine group on dopamine-PEI film surface could be determinate by SSAO in vitro and generated formaldehyde, methylglyoxal, hydrogen peroxide and ammonia [50,53].…”