Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Via C. Valeria - Gazzi, 98100 Messina, Italy.
Biochem Pharmacol. 2011 Mar 1;81(5):636-48. doi: 10.1016/j.bcp.2010.12.006. Epub 2010 Dec 11.
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.
NADPH 氧化酶是一种负责产生活性氧物种 (ROS) 的酶，抑制这种酶是治疗许多疾病的有吸引力的治疗靶点。本研究的目的是研究 NADPH 氧化酶抑制剂 apocynin 在角叉菜胶诱导性胸膜炎小鼠模型中的作用。将角叉菜胶注射到小鼠的胸膜腔中会引发急性炎症反应，其特征为：肺组织中中性粒细胞浸润，随后发生脂质过氧化，肿瘤坏死因子-α (TNF-α) 和白细胞介素-1β (IL-1β) 的产生增加，细胞间黏附分子 (ICAM-1) 和血小板黏附分子 (P-选择素) 的表达增加。此外，角叉菜胶诱导核因子-κB (NF-κB) 诱导型一氧化氮合酶 (iNOS)、硝基酪氨酸、聚 ADP-核糖聚合酶 (PARP) 的表达，并在肺组织中诱导细胞凋亡 (TUNEL 染色、FAS 配体表达、Bax 和 Bcl-2 表达) 和丝裂原活化蛋白激酶 (MAPK) 的激活。在角叉菜胶挑战后 30 分钟给予 apocynin 可显著降低所测量的所有炎症参数。因此，基于这些发现，我们提出 NADPH 氧化酶抑制剂如 apocynin 可能对治疗各种炎症性疾病有用。
