Protective effects of melatonin in zymosan-activated plasma-induced paw inflammation.
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 microg/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 microg/paw) reduced the appearance of nitrotyrosine in the tissues. Our findings support the view that melatonin exerts anti-inflammatory effects.
Costantino
G
G
Institute of Pharmacology, School of Medicine, University of Messina, Italy.
Cuzzocrea
S
S
Mazzon
E
E
Caputi
A P
AP
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015415:Biomarkers; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000517:prevention & control; D005528:Foot; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009566:Nitrates / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism*; D010949:Plasma / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D016166:Free Radical Scavengers; D009566:Nitrates; D016877:Oxidants; C039642:peroxynitric acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D008550:Melatonin