Protective effects of poly (ADP-ribose) synthase inhibitors in zymosan-activated plasma induced paw edema

The aim of the present study was to investigate the role of poly (ADP-ribos e) synthetase (PARS) in a model of acute local inflammation (zymosan-activa ted plasma (ZAP)-induced paw edema), in which the oxyradicals, nitric oxide and peroxynitrite, are known to play a crucial role. Injection of zymosan- activated plasma (ZAP) into the rat paw induced edema formation. The maxima l increase in paw volume was observed at three hours after administration ( maximal in paw volume. 1.29+/-0.09 ml). At this time point, there was a mar ked increase in neutrophil infiltration in the paw, as measured by an incre ase in myeloperoxidase (MPO) activity in the paw tissue (260+/-25 mU/100 mg wet tissue). However, ZAP-induced paw edema was significantly reduced in a dose-dependent manner by treatment with 3-aminobenzamide (3-AB) or nicotin amide (NIC), two inhibitors of PARS, at 1, 2, 3, 4 hours after ZAP injectio n. PARS inhibition also caused a significant reduction of MPO activity. The paw tissues were also examined immunohistochemically for the presence of n itrotyrosine (a footprint for peroxynitrite formation). At 3 h following ZA P injection, staining for nitrotyrosine were also found to be localised wit hin discrete cells in the inflamed paw tissue. Treatment with PARS inhibito r prevented the appearance of nitrotyrosine in the tissues. Our results sug gest that in paw edema induced by ZAP, inhibition of PARS exert potent anti inflammatory effects.