Increased Levels of Markers of Protein Oxidation in Bronchoalveolar Lavage Fluid from Patients With ARDS
The formation of reactive oxygen species (ROS), leading to increased oxidative stress has been implicated as a contributing factor to the development and progression of ARDS. Evidence of increased oxidative damage to lipids and proteins has been found in the plasma of patients with ARDS, together with low or compromised antioxidant protection. Oxidative damage to proteins and glutathione has also been observed in bronchoalveolar lavage fluid (BALF) from these patients. Plasma and BALF from ARDS patients can often have increased pro-oxidant levels. Thus, the presence of redox active iron (a catalyst for the production of reactive radicals) has been detected. Hypoxanthine (a substrate for the ROS producing enzyme xanthine oxidase) is also elevated in these patients, particularly non-survivors. ROS can arise in vivo in patients with ARDS by inflammatory cell activation, ischemia-reperfusion, and treatment with high FiO2. These processes can ultimately result in the formation of damaging ROS, such as peroxynitrite, hypochlorous acid, and the hydroxyl radical. Direct measurement of highly reactive species is not possible because of their transient nature. However, measurement of characteristic patterns of damage to biological molecules can provide evidence of their formation. We have therefore measured markers of ROS formation as:-(chlorotyrosine for hypochlorous acid, nitrotyrosine for peroxynitrite, and ortho-tyrosine for hydroxyl radicals) in BALF proteins from patients with ARDS, as well as in ventilated post operative intensive care patients, and normal healthy controls. Neutrophil activation in BALF was determined by measuring myleoperoxidase (MPO) levels. Our aim was to establish whether ROS neutrophil activation was the dominant source of ROS in patients with ARDS.