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 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.
Department of Biomorphology, School of Medicine, University of Messina, Messina, Italy.
E
E
Mazzon
I
I
Serraino
J H
JH
Li
L
L
Dugo
A P
AP
Caputi
J
J
Zhang
S
S
Cuzzocrea
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000517:prevention & control; D001578:Benzopyrans / Q000494:pharmacology*; D002351:Carrageenan / Q000008:administration & dosage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006614:Hindlimb; D007249:Inflammation / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control*; D007546:Isoquinolines / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D015996:Survival Rate; D015054:Zymosan / Q000008:administration & dosage
D000893:Anti-Inflammatory Agents; D001578:Benzopyrans; D004791:Enzyme Inhibitors; C417259:GPI 6150; D007546:Isoquinolines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D002351:Carrageenan; D015054:Zymosan; D011065:Poly(ADP-ribose) Polymerases