Hyperoxia and paraquat ingestion are 2 clinical examples of lung injury thought to be mediated by oxidant mechanisms. An in vitro cytotoxicity assay using freshly explanted 51Cr-lung tissue as the target was used to quantify the ability of hyperoxia and paraquat to directly injure lung parenchymal cells in an environment where indirect mechanisms such as recruitment of inflammatory cells were not possible. There were clear species differences in the susceptibility of lung parenchyma to direct injury by hyperoxia (95% O2) and paraquat (10 .mu.M-10 mM) for 18 h at 37.degree. C, with human and rat lung being more sensitive than rabbit lung. O2 radical inhibitors, particularly catalase (1100 U/ml) and .alpha.-tocopherol (10 .mu.g/ml), reduced hyperoxia and paraquat-induced lung injury, although their ability to do so depended on the oxidant and the species. The simultaneous use of hyperoxia and paraquat accelerated the in vitro lung parenchymal cell injury in each species. O2 and paraquat directly injured the cells of the lower respiratory tract without enlisting the aid of additional blood-derived inflammatory cells. 51Cr-lung explant assay used for these studies allowed for the quantitative assessment of direct lung cell injury and may prove useful as an in vitro model by which to investigate lung injury of other etiologies.
