gpi-6150 and Edema

Poly (ADP-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 (1,11b-dihydro-[2H]benzopyrano [4,3,2-de]isoquinolin-3-one), a new poly (ADP-ribose) polymerase inhibitor, in animal models of acute and chronic inflammation (carrageenan-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 poly (ADP-ribose) polymerase inhibitor GPI 6150 inhibits the inflammatory response (paw swelling, and organ injury). The present results demonstrate that inhibition of poly (ADP-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.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Benzopyrans; Carrageenan; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Enzyme Inhibitors; Hindlimb; Inflammation; Isoquinolines; Liver; Lung; Male; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Rats; Rats, Long-Evans; Survival Rate; Zymosan