Superoxide dismutase and pulmonary oxygen toxicity: Lessons from transgenic and knockout mice (Review)

Superoxide (O-2(-)) has been implicated in the pathogenesis of pulmonary O- 2 toxicity. The studies using transgenic and knockout mice of each of the t hree isoforms of superoxide dismutase (SOD) e.g., CuZnSOD, MnSOD and extrac ellular SOD (EC-SOD), have demonstrated that O-2(-) produced in the mitocho ndria from its electron transport system and extracellular O-2(-) generated by infiltrating neutrophils, and possibly its derivatives e.g., hydroxyl r adical and peroxynitrite, are important mediators of hyperoxia-induced pulm onary injury, while cytoplasmic O-2(-) plays a limited, if any, role in the pathogenesis of pulmonary O-2 toxicity. Distal airway epithelial cells inc luding type II alveolar and non-ciliated bronchiolar epithelial cells, are important targets for O-2 radicals under the hyperoxic condition. The acces sibility of these distal airway epithelial cells to in vivo gene transfer t hrough the tracheal route of administration, suggests the potential for in vivo transfer of MnSOD and EC-SOD genes as a future approach in the prevent ion of pulmonary O-2 toxicity.