GPI 6150, a poly (ADP-ribose) polymerase inhibitor, exhibits an anti-inflammatory effect in rat models of inflammation

PolyŽADP-ribose.polymerase, a nuclear enzyme activated by DNA strand breaks, has been show to play an important role in the pathogenesis of inflammation. Here, we investigate the effects of GPI 6150 Ž1,11b-dihydro-w2Hxbenzopyranow4,3,2-dexisoquinolin-3-one., a new polyŽADP-ribose.polymerase inhibitor, in animal models of acute and chronic inflammation Žcarrageenan-induced paw edema, adjuvant-induced arthritis and zymosan-induced multiple organ failure. where oxygen radicals, nitric oxide and peroxynitrite are known to play a crucial role in the inflammatory process. The results show that the polyŽADP-ribose.polymerase inhibitor GPI 6150 inhibits the inflammatory responseŽpaw swelling, and organ injury.. The present results demonstrate that inhibition of poly ŽADP-ribose. polymerase by GPI 6150 exerts potent anti-inflammatory effects. Part of these anti-inflammatory effects may be related to a reduction of neutrophil recruitment into the inflammatory site.