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

The aim of the present study was to investigate the protective effect of th e pineal hormone melatonin in a model of acute local inflammation (zymosan- activated plasma-induced paw oedema), in which oxyradicals, nitric oxide (N O) and peroxynitrite are known to play a crucial role in the inflammatory p rocess. The intraplantar injection of zymosan-activated plasma elicited an inflammatory response that was characterized by a time-dependent increase i n paw oedema, neutrophil infiltration and increased levels of nitrite/nitra te 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 i ncreased in the zymosan-activated plasma-treated paw (226 +/- 10.2 mU/100 m g wet tissue, 31 +/- 2.1 mM/mg wet tissue, respectively). However, zymosan- activated plasma-induced paw oedema was significantly reduced in a dose-dep endent manner by treatment with melatonin (given at 62.5 and 125 mu g/paw) at 1, 2, 3, 4 h after injection of zymosan-activated plasma. Melatonin trea tment also caused a significant reduction of the myeloperoxidase activity a nd lipid peroxidation and inhibited nitrite/nitrate levels in the paw exuda te. The paw tissues were also examined immunohistochemically for the presen ce 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 mu g/paw) reduced the appearance of nitrotyrosine in the tissues. Our findings support the view that melatonin exerts anti-inflammatory effects. (C) 1998 Elsevier Science B.V. All rights reserved.