Abstract

Supraphysiological concentrations of oxygen (hyperoxia) is necessary for treatment or prevention of hypoxemic condition, but hyperoxia through activation of oxidative stress pathways and generation of reactive oxygen species directly or indirectly result in lung injury and dysfunction. Many mediators are involved in the pathways to hyperoxic cell death seeming that transition metal ions especially iron promote the generation of the very reactive free radicals which are damaging to cells. Thus concerning the role of iron, a systematic review was conducted by reviewing all papers found from searching keywords of iron, lung injury, oxidative stress or hyperoxia in bibliography databases. Due to different pathways involved in hyperoxia-induced lung injury, several classes of drugs have been tested for example antioxidants, dexamethasone, pentoxifylline, erythropoietin, lisofylline, sildenafile, N-acetyl cysteine, or prostaglandine but some of them were not only successful but caused significant adverse effects. Findings indicate that metal ions especially iron through catalyzing of most reactive free radicals has a key role in oxidative stress process and hyperoxic condition and thus limitation of iron for prevention of hyperoxia-induced injury seems reasonable. Iron chelation has been recently used for conditions without iron overload such as neurodegenerative, infectious, reperfusion injury, cardioprotection. There are some evidences about positive effects of desferrioxamine alone or in combination when tested in animal models of lung injury or in human but they are not convincing. Further studies are necessary to clarify the importance of intervention with desferrioxamine or new long acting oral agent deferasirox and their risk/benefit in hyperoxia-induced lung injury.