ArticleRheumatology (Oxford, England)2016
Effects of the neutrophil elastase inhibitor EL-17 in rat adjuvant-induced arthritis.
Article in Rheumatology (Oxford, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- Regulation of the innate immune response in rheumatoid arthritis.Frontiers in immunology · 2025Review
- Neutrophils in Inflammatory Diseases: Unraveling the Impact of Their Derived Molecules and Heterogeneity.Cells · 2023Review
- Protective and Pain-Killer Effects of AMC3, a Novel N-Formyl Peptide Receptors (FPRs) Modulator, in Experimental Models of Rheumatoid Arthritis.Antioxidants (Basel, Switzerland) · 2023Article
- Spectrofluorimetric and Computational Investigation of New Phthalimide Derivatives towards Human Neutrophil Elastase Inhibition and Antiproliferative Activity.International journal of molecular sciences · 2022Article
- Sulfonated Nonsaccharide Heparin Mimetics Are Potent and Noncompetitive Inhibitors of Human Neutrophil Elastase.ACS omega · 2021Article
- Novel formyl peptide receptor (FPR) agonists with pyridinone and pyrimidindione scaffolds that are potentially useful for the treatment of rheumatoid arthritis.Bioorganic chemistry · 2020Article
- Ahp-Cyclodepsipeptide Inhibitors of Elastase: Lyngbyastatin 7 Stability, Scalable Synthesis, and Focused Library Analysis.ACS medicinal chemistry letters · 2020Article
- Novel Sulfonamide Analogs of Sivelestat as Potent Human Neutrophil Elastase Inhibitors.Frontiers in chemistry · 2020Article
- A patenting perspective on human neutrophil elastase (HNE) inhibitors (2014-2018) and their therapeutic applications.Expert opinion on therapeutic patents · 2019Review
- Protease Inhibitors in Tick Saliva: The Role of Serpins and Cystatins in Tick-host-Pathogen Interaction.Frontiers in cellular and infection microbiology · 2017Review
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
objectivesNeutrophil elastase (NE), a granule-associated enzyme, participates in connective tissue breakdown and promotes cytokine release and specific receptor activation during various inflammatory diseases like RA. NE is increased in the SF and cartilage of RA patients and represents a target for the development of new therapeutic possibilities. The present research aimed to evaluate the preclinical pharmacological profile of the N-benzoylpyrazole derivative EL-17, a potent and selective NE inhibitor, in a rat model of RA.
methodsComplete Freund's Adjuvant (CFA) was injected in the tibiotarsal joint and the effect of acute or repeated treatments with EL-17 (1-30 mg/kg by mouth) were evaluated.
resultsOn day 14 after CFA injection, a single administration of EL-17 significantly reduced CFA-dependent hypersensitivity to mechanical noxious stimuli and the postural unbalance related to spontaneous pain. To evaluate the preventive efficacy, EL-17 was administered daily starting from the day of CFA treatment. Behavioural measurements performed on days 7 and 14 showed a progressive efficacy of EL-17 against hypersensitivity to mechanical noxious and non-noxious stimuli, as well as a decrease of hind limb weight-bearing alterations. Histological evaluation of the tibiotarsal joint (day 14) demonstrated significant prevention of articular derangement after EL-17 (30 mg/kg) treatment. The protective effects of EL-17 directly correlated with a complete reversion of the plasma NE activity increase induced by CFA.
conclusionsThe NE inhibitor EL-17 relieved articular pain after acute administration. Furthermore, repeated treatment reduced the development of hypersensitivity and protected joint tissue, revealing a disease-modifying profile.
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