Redox control of asthma: molecular mechanisms and therapeutic opportunities.
An imbalance in reducing and oxidizing (redox) systems favoring a more oxidative environment is present in asthma and linked to the pathophysiology of the defining symptoms and signs including airflow limitation, hyper-reactivity, and airway remodeling. High levels of hydrogen peroxide, nitric oxide ((*)NO), and 15-F(2t)-isoprostane in exhaled breath, and excessive oxidative protein products in lung epithelial lining fluid, peripheral blood, and urine provide abundant evidence for pathologic oxidizing processes in asthma. Parallel studies document loss of reducing potential by nonenzymatic and enzymatic antioxidants. The essential first line antioxidant enzymes superoxide dismutases (SOD) and catalase are reduced in asthma as compared to healthy individuals, with lowest levels in those patients with the most severe asthma. Loss of SOD and catalase activity is related to oxidative modifications of the enzymes, while other antioxidant gene polymorphisms are linked to susceptibility to develop asthma. Monitoring of exhaled (*)NO has entered clinical practice because it is useful to optimize asthma care, and a wide array of other biochemical oxidative and nitrative biomarkers are currently being evaluated for asthma monitoring and phenotyping. Novel therapeutic strategies that target correction of redox abnormalities show promise for the treatment of asthma.
Comhair
Suzy A A
SA
Pathobiology, Lerner Research Institute, and the Respiratory Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA. comhais@ccf.org
Erzurum
Serpil C
SC
D001249:Asthma / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000201:enzymology / Q000378:metabolism; D010084:Oxidation-Reduction; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D002374:Catalase; D013482:Superoxide Dismutase