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Treatment with Quinoline-3-carboxamide does not successfully prevent immune-mediated glomerulonephritis in mice

Draibe, J; Pepper, RJ; Salama, AD; (2016) Treatment with Quinoline-3-carboxamide does not successfully prevent immune-mediated glomerulonephritis in mice. Nefrología , 36 (6) pp. 687-693. 10.1016/j.nefro.2016.03.012. Green open access

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Abstract

Introduction: Quinoline-3-carboximide compounds, such as paquinimod, which targets the protein S100A9, have demonstrated efficacy in treating autoimmune diseases. S100A9, in association with S100A8, forms the heterodimer S100A8/S100A9, known as calprotectin; that has been shown to be upregulated in numerous inflammatory disorders. We had previously demonstrated protection from glomerular disease in S100A9-deficient mice. The aim of this study was to assess the efficacy of paquinimod in the prevention and treatment of experimental glomerulonephritis. Methods: Nephrotoxic nephritis (NTN) was induced in C57BL/6 mice according to our standard protocol. Mice were treated with different doses of paquinimod either at disease induction (prevention group) or two days following induction (therapeutic group) and sacrificed 8 days following induction. Disease was assessed histologically (number of glomerular crescents, degree of glomerular thrombosis, number of infiltrating leucocytes and calprotectin expression) and biochemically (serum creatinine and urea levels, and urinary levels of protein). Results: Neither treatment with low (0.5 mg/kg) or high (25 mg/kg) doses of paquinimod, given preventatively or therapeutically, led to disease attenuation, as assessed by biochemical or histological parameters. Additionally, we found trends for an increase in renal glomerular calprotectin expression in the high dose groups, suggesting a possible feedback regulation of calprotectin expression. Conclusions: Our results show that paquinimod does not successfully prevent or treat mice with NTN. Other models of immune-mediated glomerulonephritis need to be tested to investigate the therapeutic potential of this compound in renal disease.

Type: Article
Title: Treatment with Quinoline-3-carboxamide does not successfully prevent immune-mediated glomerulonephritis in mice
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.nefro.2016.03.012
Publisher version: http://doi.org/10.1016/j.nefro.2016.03.012
Language: English
Additional information: Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: Glomerulonephritis, Animal model, Calprotectin, Paquinimod
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1541101
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