Protective Effects of the Lazaroid U-74389G Against Hyperoxia in Rat Type II Pneumocytes

Abstract The aims of this study were to investigate the effect of hyperoxia on O 2 −· , H 2 O 2 and · NO generation and iNOS mRNA levels in rat type II pneumocytes in vitro and the possible protective effect of the lazaroid U-74389G. Rat type II pneumocytes were exposed, 36 h after isolation, to air, 60% or 85% O 2 for 48 h. At the beginning of the experiment and 24 h later, the cells were exposed for 30 min to either 30 μ m U-74389G or only the vehicle for the lazaroid (control). Exposure to 60% and 85% O 2 decreased nitrite production 2.9-fold and 3.9-fold, and increased O 2 −· and H 2 O 2 generation 4.6-fold and 6.7-fold, respectively. In the 85% O 2 -exposed cells, hyperoxia increased lipid peroxidation (thiobarbituric acid reactive substances, TBARS production) 2-fold and iNOS mRNA production 5.4-fold. U-74389G prevented the decrease in nitrite and the rise in O 2 −· and H 2 O 2 production, the increase in TBARS and the rise in iNOS mRNA after hyperoxia. We conclude that exposure of type II pneumocytes in vitro to subtoxic oxygen levels leads to a disturbance in the · NO-O 2 −· balance despite increased iNOS mRNA levels. The lazaroid U-74389G appears to be a useful compound in the protection of hyperoxic lung injury by restoration of this · NO-O 2 −· balance and prevention of TBARS formation.