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

16 Citations (Scopus)

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

Fingerprint

Pleurisy
Carrageenan
Low Molecular Weight Heparin
Anti-Inflammatory Agents
Celecoxib
Inflammation
Pharmaceutical Preparations
Heparin
Glucuronic Acid
Coagulants
Thiobarbituric Acid Reactive Substances
Cyclooxygenase 2 Inhibitors
Disaccharides
Lung Injury
Therapeutic Uses
Nitric Oxide Synthase Type II
Exudates and Transudates
Cyclooxygenase 2
Interleukin-1
Prostaglandins

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

Cite this

Anti-inflammatory effects of low molecular weight heparin derivative in a rat model of carrageenan-induced pleurisy. / Ceccarelli, Matteo; Bani, Daniele; Cinci, Lorenzo; Nistri, Silvia; Uliva, Caterina; Ragazzo, Elena; Vannacci, Alfredo; Manoni, Marco; Gori, Anna Maria; Abbate, Rosanna; Gensini, Gian Franco; Masini, Emanuela.

In: Journal of Cellular and Molecular Medicine, Vol. 13, No. 8 B, 08.2009, p. 2704-2712.

Research output: Contribution to journalArticle

Ceccarelli, M, Bani, D, Cinci, L, Nistri, S, Uliva, C, Ragazzo, E, Vannacci, A, Manoni, M, Gori, AM, Abbate, R, Gensini, GF & 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, vol. 13, no. 8 B, pp. 2704-2712. https://doi.org/10.1111/j.1582-4934.2009.00658.x
Ceccarelli, Matteo ; Bani, Daniele ; Cinci, Lorenzo ; Nistri, Silvia ; Uliva, Caterina ; Ragazzo, Elena ; Vannacci, Alfredo ; Manoni, Marco ; Gori, Anna Maria ; Abbate, Rosanna ; Gensini, Gian Franco ; Masini, Emanuela. / Anti-inflammatory effects of low molecular weight heparin derivative in a rat model of carrageenan-induced pleurisy. In: Journal of Cellular and Molecular Medicine. 2009 ; Vol. 13, No. 8 B. pp. 2704-2712.
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