Protective effects of melatonin in zymosan-activated plasma-induced paw inflammation

Giuseppina Costantino, Salvatore Cuzzocrea, Emanuela Mazzon, Achille P. Caputi

Research output: Contribution to journalArticlepeer-review


The aim of the present study was to investigate the protective effect of the pineal hormone melatonin in a model of acute local inflammation (zymosan-activated plasma-induced paw oedema), in which oxyradicals, nitric oxide (NO) and peroxynitrite are known to play a crucial role in the inflammatory process. The intraplantar injection of zymosan-activated plasma elicited an inflammatory response that was characterized by a time-dependent increase in paw oedema, neutrophil infiltration and increased levels of nitrite/nitrate in the paw exudate. The maximal increase in paw volume was observed at 3 h after administration (maximal in paw volume: 1.34±0.09 ml). At this time point, myeloperoxidase activity and lipid peroxidation were markedly increased in the zymosan-activated plasma-treated paw (226±10.2 mU/100 mg wet tissue, 31±2.1 mM/mg wet tissue, respectively). However, zymosan-activated plasma-induced paw oedema was significantly reduced in a dose-dependent manner by treatment with melatonin (given at 62.5 and 125 μg/paw) at 1, 2, 3, 4 h after injection of zymosan-activated plasma. Melatonin treatment also caused a significant reduction of the myeloperoxidase activity and lipid peroxidation and inhibited nitrite/nitrate levels in the paw exudate. The paw tissues were also examined immunohistochemically for the presence of nitrotyrosine (a marker of peroxynitrite formation). At 3 h following injection of zymosan-activated plasma, staining for nitrotyrosine was also found to be localised in the inflamed paw tissue. Treatment with melatonin (125 μg/paw) reduced the appearance of nitrotyrosine in the tissues. Our findings support the view that melatonin exerts anti-inflammatory effects. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)57-63
Number of pages7
JournalEuropean Journal of Pharmacology
Issue number1
Publication statusPublished - Dec 11 1998


  • Melatonin
  • Nitric oxide (NO)
  • Oedema
  • Peroxynitrite
  • Zymosan-activated plasma

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology


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