Anti-inflammatory effects of low molecular weight heparin derivative in a rat model of carrageenan-induced pleurisy

Matteo Ceccarelli, Daniele Bani, Lorenzo Cinci, Silvia Nistri, Caterina Uliva, Elena Ragazzo, Alfredo Vannacci, Marco Manoni, Anna Maria Gori, Rosanna Abbate, Gian Franco Gensini, Emanuela Masini

Research output: Contribution to journalArticle

Abstract

Summary Low molecular weight heparin derivatives are characterized by low anti-coagulant activity and marked anti-inflammatory effects that allow for these molecules to be viewed as a new class of non-steroidal anti-inflammatory drugs (NSAIDs). We show here that K5NOSepiLMW, an O-sulphated heparin-like semi-synthetic polymer of the D-glucuronic acid-N-acetyleparoson disaccharide unit with low molecular weight, has marked anti-inflammatory effects in a rat model of acute inflammation, the carrageenan-induced pleurisy, commonly used to test NSAID efficacy. A 30-min. pre-treatment with K5NOSepiLMW (0.1, 0.5 and 1 mg/kg b.wt., given intrapleurally) attenuated the recruitment of leucocytes in the lung tissue and the pleural exudate, inhibited the induction of inducible nitric oxide synthase and cyclooxygenase-2 (COX-2), thereby abating the generation of nitric oxide and pro-inflammatory prostaglandins such as PgE 2 and PGF, reduced the inflammation-induced nitroxidative lung tissue injury, as shown by tissue thiobarbituric acid-reactive substances and nitrotyrosine, and blunted the local generation of cytokines such as interleukin-1β and tumour necrosis factor-α. All these parameters were markedly increased by intrapleural carrageenan in the absence of any pre-treatment. The anti-inflammatory action of K5NOSepiLMW is specific, as judged by the lack of therapeutic effects of B4/110, a biologically inactive cognate polysaccharide, given in the place of the authentic molecule. Moreover, K5NOSepiLMW showed similar effects as celecoxib (1 mg/kg b.wt), a COX-2 inhibitor and well-known NSAID. This study provides further insight into the mechanisms underlying the beneficial effects of heparin derivatives in inflammation and identifies K5NOSepiLMW as a novel, promising anti-inflammatory drug.

Original languageEnglish
Pages (from-to)2704-2712
Number of pages9
JournalJournal of Cellular and Molecular Medicine
Volume13
Issue number8 B
DOIs
Publication statusPublished - Aug 2009

Keywords

  • Cyclooxygenase-2
  • Cytokines
  • Leucocytes
  • Low molecular weight heparin
  • Nitric oxide synthase
  • Pleurisy

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

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  • Cite this

    Ceccarelli, M., Bani, D., Cinci, L., Nistri, S., Uliva, C., Ragazzo, E., Vannacci, A., Manoni, M., Gori, A. M., Abbate, R., Gensini, G. F., & Masini, E. (2009). Anti-inflammatory effects of low molecular weight heparin derivative in a rat model of carrageenan-induced pleurisy. Journal of Cellular and Molecular Medicine, 13(8 B), 2704-2712. https://doi.org/10.1111/j.1582-4934.2009.00658.x