Effect of apocynin, a NADPH oxidase inhibitor, on acute lung inflammation

Abstract

NADPH-oxidase is an enzyme responsible for reactive oxygen species production (ROS) and inhibition of this enzyme represents an attractive therapeutic target for the treatment of many diseases. The aim of this study was to investigate the effects of apocynin, a NADPH-oxidase inhibitor, in a mouse model of carrageenan-induced pleurisy. Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterized by: infiltration of neutrophils in lung tissues and subsequent lipid peroxidation, increased production of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and increased expression of intercellular adhesion molecule (ICAM-1) and platelet-adhesion molecule (P-selectin). Furthermore, carrageenan induced the expression of nuclear factor-κB (NF-κB) inducible nitric oxide synthase (iNOS), nitrotyrosine, poly-ADP-ribosyl polymerase (PARP) as well as induced apoptosis (TUNEL staining, FAS-ligand expression, Bax and Bcl-2 expression) and mitogen-activated protein kinase (MAPK) activation in the lung tissues. Administration of apocynin, 30min after the challenge with carrageenan, caused a significant reduction of all the parameters of inflammation measured. Thus, based on these findings we propose that NADPH oxidase inhibitor such as apocynin may be useful in the treatment of various inflammatory diseases.