%0 Journal Article
%T Simulating Sleep Apnea by Exposure to Intermittent Hypoxia Induces Inflammation in the Lung and Liver
%A Darlan Pase da Rosa
%A Luiz Felipe Forgiarini
%A Diego Baronio
%A Cristiano Andrade Feij車
%A D那nis Martinez
%A Norma Possa Marroni
%J Mediators of Inflammation
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/879419
%X Sleep apnea is a breathing disorder that results from momentary and cyclic collapse of the upper airway, leading to intermittent hypoxia (IH). IH can lead to the formation of free radicals that increase oxidative stress, and this mechanism may explain the association between central sleep apnea and nonalcoholic steatohepatitis. We assessed the level of inflammation in the lung and liver tissue from animals subjected to intermittent hypoxia and simulated sleep apnea. A total of 12 C57BL/6 mice were divided into two groups and then exposed to IH ( ) or a simulated IH (SIH) ( ) for 35 days. We observed an increase in oxidative damage and other changes to endogenous antioxidant enzymes in mice exposed to IH. Specifically, the expression of multiple transcription factors, including hypoxia inducible factor (HIF-1 ), nuclear factor kappa B (NF- B), and tumor necrosis factor (TNF- ), inducible NO synthase (iNOS), vascular endothelial growth factor (VEGF), and cleaved caspase 3 were shown to be increased in the IH group. Overall, we found that exposure to intermittent hypoxia for 35 days by simulating sleep apnea leads to oxidative stress, inflammation, and increased activity of caspase 3 in the liver and lung. 1. Introduction Obstructive sleep apnea (OSA) consists of sleep-disordered breathing. Cyclic episodes result in the momentary closure, partial or complete, of the upper airway at the level of the pharynx. The repeated pauses in breathing can lead to intermittent hypoxia (IH) and increased reactive oxygen species (ROS) [1]. The increase of ROS in OSA is likely due to the repeated oxygen depletion followed by the hyperoxia that develops to restore oxygen pressure (PO2). A similar phenomenon is observed in ischemia followed by reperfusion [2每5]. In ischemia/reperfusion, xanthine oxidase generates free radicals in the presence of oxygen, contributing to oxidative stress [6每8]. OSA is associated with chronic liver diseases, such as nonalcoholic steatohepatitis (NASH) [9每16]. Savransky and colleagues demonstrated that IH can act as a ※second hit§ to liver disease by amplifying the tissue damage induced by a high dose of paracetamol [17, 18]. The injury mechanism, triggered by OSA, appears to be related to the formation of peroxynitrite, depletion of glutathione, and apoptosis of hepatocytes [18]. In OSA, inflammatory factors, such as nuclear factor kappa B (NF-百B), are activated at a systemic level [17, 19]. NF-百B is a master regulator of the inflammatory process, by inhibiting its inhibitor IKK-b, and its activation leads to the increased expression of tumor
%U http://www.hindawi.com/journals/mi/2012/879419/