Abstract
Apocynin is a potent and selective inhibitor of the NADPH oxidase-dependent production of ROS by stimulated human PMNs. Apocynin was isolated by activity-guided isolation from Picrorhiza kurroa, and in the years following its discovery it has been used in many laboratories around the world. Reactive oxygen species (ROS) production by activated polymorphonuclear neutrophils (PMNs) plays an important role in many cardiovascular disease states, including myocardial ischemia reperfusion injury. The purpose of this study is to examine the beneficial effects of apocynin on myocardial ischemia reperfusion injury. Myocardial I/R injury was caused by clamping the left anterior descending (LAD) coronary artery for 20 min followed by release of the clamp allowing reperfusion for 1 h. Administration of apocynin i.p. (5mg/kg i.p. 10%DMSO) 15 min after ischemia significantly reduced the: 1) histological evidence of myocardial injury; 2) pro-inflammatory cytokines (TNF-α, IL-1β); 3) adhesion molecules (ICAM-1, P-Selectin); 4) nitrotyrosine formation; 5) NF-kB expression; 6) PAR formation; and 7) apoptosis (Bax, Bcl-2, Fas-L and tunel). Based on these findings we propose that apocynin would be useful in the treatment of various ischemia and reperfusion diseases.