Mazzon E, Serraino I, Li J H, Dugo L, Caputi A P, Zhang J, Cuzzocrea S
Department of Biomorphology, School of Medicine, University of Messina, Messina, Italy.
Eur J Pharmacol. 2001 Mar 9;415(1):85-94. doi: 10.1016/s0014-2999(01)00809-3.
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.
聚（ADP - 核糖）聚合酶是一种由DNA链断裂激活的核酶，已被证明在炎症发病机制中起重要作用。在此，我们研究了新型聚（ADP - 核糖）聚合酶抑制剂GPI 6150（1,11b - 二氢 - [2H]苯并吡喃并[4,3,2 - de]异喹啉 - 3 - 酮）在急性和慢性炎症动物模型（角叉菜胶诱导的爪肿胀、佐剂诱导的关节炎和酵母聚糖诱导的多器官衰竭）中的作用，在这些模型中，氧自由基、一氧化氮和过氧亚硝酸盐在炎症过程中起关键作用。结果表明，聚（ADP - 核糖）聚合酶抑制剂GPI 6150抑制炎症反应（爪肿胀和器官损伤）。目前的结果表明，GPI 6150对聚（ADP - 核糖）聚合酶的抑制作用具有强大的抗炎效果。这些抗炎作用部分可能与减少中性粒细胞向炎症部位的募集有关。
