Protective effects of apocynin, an inhibitor of NADPH oxidase activity, in splanchnic artery occlusion and reperfusion

Abstract

SAO shock is a severe form of circulatory shock produced by I/R of the splanchnic organs. SAO causes an enhanced formation of ROS, which contributes to the pathophysiology of shock. Apocynin is a naturally occurring, methoxy-substituted catechol, experimentally used as an inhibitor of NOX. It can decrease the production of ROS from activated neutrophils and macrophages, inhibiting the assembly of NADPH-oxidase activity. In this study, we wanted to evaluate the pharmacological action of apocynin in rats subjected to SAO shock, which was induced by clamping the superior mesenteric artery and the celiac trunk, resulting in a total occlusion of these arteries for 45 min. After this period of occlusion, the clamps were removed. Administration of apocynin i.p. (5 mg/kg i.p. 10% DMSO) 5 min before reperfusion significantly reduced the (1) histological evidence of tissue injury, (2) proinflammatory cytokine production (TNF-α, IL-1β), (3) adhesion molecules (ICAM-1, P-selectin), (4) nitrotyrosine formation, (5) NF-κB expression, and (6) apoptosis (Bax, Bcl-2, Fas-L, and TUNEL). These results could imply a future use of apocynin in the treatment of I/R shock.