[Therapy of lung diseases with anti-oxidants]

Oxidants, highly reactive free radicals, play a major role in the pathogenesis of a variety of inflammatory lung disorders. In the healthy lung, the oxidant burden is balanced by the local antioxidant defenses. However, both an increased oxidant burden and/or decreased antioxidant defenses may reverse the physiological oxidant-antioxidant balance in favour of oxidants, leading to lung injury. This concept points to an obvious therapeutic strategy: augmentation of the antioxidant screen of the lung to prevent oxidant-mediated tissue damage. Studies using reduced glutathione (GSH), the major pulmonary antioxidant, as a model therapeutic agent demonstrate that GSH can be administered directly to the respiratory epithelial surface by aerosol and is fully functional as an antioxidant both in vitro and in vivo. In pulmonary diseases such as idiopathic pulmonary fibrosis or following HIV-infection GSH aerosol therapy not only normalises deficient pre-therapy GSH-levels in the lung, but is capable of favourably influencing cellular events such as oxidant release by pulmonary inflammatory cells. These results suggest that it is possible to use antioxidants to reverse the imbalance between oxidants and antioxidants at the site of oxidant injury to prevent the progressive tissue damage in lung disorders characterised by high oxidant states.