Mechenism Of Oxidative Damage And Antioxidant Therapeutic Advances In Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis is defined as a specific form of chronic, diffused fibrosing interstitial pneumonia of unknown cause.It is characterized by progressive worsening of dyspnea and lung function and is associated with a poor prognosis,and patients finally died of respiratory failure.The incidence of IPF is rising in recent years.Oxidants include superoxide, hydroxyl radicals,hydrogen peroxide, nitric oxide and peroxynitrite can be generated in the lung,among which hydroxyl radicals is the most detrimental.Antioxidants comprise vitamin E, a-lipoic acid, glutathione,superoxide dismutase,catalase,glutathione peroxidase,heme oxygenase1,thioredoxins,et al.Antioxidants can scavenge oxidants or catalyze them to less detrimental forms lest they cause oxidative damage.Oxidative damage play an important role in the process of IPF,which makes it necessary to keep the balance of redox.Oxidants inhibit the development of IPF through following mechanisms. Oxidants such as ROS can damage proteins,DNA and lipids directly.Besides,Oxidants activate NF-κB and AP-1,which subsequently induces gene expression of inflammatory factors such as IL-1,TNF-α and TGF-β1.IL-1and TNF-α can activate NF-κB and TGF-β1can increase products of ROS in the meantime,which forms positive feedback. TGF-β1is capable of decreasing the generation of PGE2and increasing the generation of LT and TXA2.PGE2has a capacity for inhibiting pulmonary fibrosis while the later aggravating pulmonary fibrosis,which leads to inflammatory injury.Fibroblast stimulated tends to transform to myofibroblast,which is the key cell to synthesis and secrete extracellular matrix.The imbalance of protein/antiprotease,taking matrix metalloproteinases/inhibitors of metalloproteinase for example,can lead to excessive deposition of extracellular matrix.Increased ROS contribute to apoptosis of alveolar epithelial cell,which leads to damage of alveolar basement membrane and recruit fibroblast.The deposition of extracellular matrix finally destroy lung structure.In summary,correct the imbalance of oxidants and antioxidants is beneficial to alleviate its symptoms and slow down the development of IPF.Antioxidant therapy is promising in the treatment of IPF.There are no effective drugs to cure IPF,the effect of hormone and immunosuppressive agents is dissatisfied, therefore it is urgent to develop new drugs or hunt for new methods.Currently, drugs of experimental therapy for IPF include nonenzyme antioxidant, enzyme antioxidant and Chinese Herbal. Althrough NAC, ambroxol hydrochloride and a-lipoic acid are used to treat IPF, but therapeutic effect is not sure and they need to additional Clinical Trials.In this review,we summarizes lots of domestic and foreign literature and gives a detailed introduction about advances in oxidants and antioxidants in the lung, pathogenesis of oxidative damage, antioxidant therapy,summary and outlook.In the end, there is a review of therapeutic advances in idiopathic pulmonary fibrosis.