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

Poly (ADP-ribose) polymerase, a nuclear enzyme activated by DNA strand brea ks, has been show to play an important role in the pathogenesis of inflamma tion. Here, we investigate the effects of GPI 6150 (1,11b-dihydro-[2H]benzo pyrano [4,3,2-de]isoquinolin-3-one), a new poly (ADP-ribose) polymerase inh ibitor, in animal models of acute and chronic inflammation (carrageenan-ind uced paw edema, adjuvant-induced arthritis and zymosan-induced multiple org an failure) where oxygen radicals, nitric oxide and peroxynitrite are known to play a crucial role in the inflammatory process. The results show that the poly (ADP-ribose) polymerase inhibitor GPI 6150 inhibits the inflammato ry response (paw swelling, and organ injury). The present results demonstra te that inhibition of poly (ADP-ribose) polymerase by GPI 6150 exerts poten t anti-inflammatory effects. Part of these anti-inflammatory effects may be related to a reduction of neutrophil recruitment into the inflammatory sit e. (C) 2001 Published by Elsevier Science B.V.