Time course of inflammation, oxidative stress and tissue damage induced by hyperoxia in mouse lungs (original) (raw)

2012, International Journal of Experimental Pathology

Acute lung injury (ALI) affects a large number of patients worldwide, with reported mortality rates of 35-40% (Rubenfeld & Herridge 2007). Many patients with ALI require oxygen supplementation to maintain adequate tissue oxygenation, leading to hyperoxia (Fisher & Beers 2008). However, exposure to hyperoxia can have pathological effects, such as lung inflammation and oedema accompanied by epithelial and endothelial cell death, suggesting that oxygen supplementation, although necessary, may potentially perpetuate or exacerbate ALI (Bhandari et al. 2006; Bhandari 2008). Paradoxically, hyperoxia may cause ALI and damage to components of the extracellular matrix (Murray et al. 2008). Moreover, hyperoxia has been linked to the production of reactive oxygen species (ROS) and subsequent oxida-tive stress (Huang et al. 2009). Reactive oxygen species are important mediators in ALI, attacking biological molecules and causing lipid peroxidation, protein oxidation and DNA breakage (Papaiahgari et al. 2006). Under physiological conditions, living organisms maintain a balance between the formation and removal of ROS (Owuor & Kong 2002). The antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase and non-enzymatic antioxidants, such as a-tocopherol, vitamin-C, carotenoids and the glutathione system, all prevent the formation of toxic levels of ROS. Oxidative stress occurs when the generation of ROS in a system exceeds the system's capacity to neutralize and eliminate the ROS (Sies 1997