Previous studies in our lab have shown that F344 rats are more susceptible to hyperoxic lung injury than are Sprague Dawley (SD) rats. This increased susceptibility to hyperoxic lung injury is accompanied by the accumulation of iron in the bronchoalveolar lavage. We hypothesized that the greater susceptibility to hyperoxic lung injury seen in F344 rats is due to this strain's relatively poor ability to compartmentalize cellular iron, leading to increased amounts of redox-active iron in the lung. We hypothesized that although SD rats are better able to maintain cellular iron homeostasis, the protective mechanisms may be overwhelmed with acute iron dosing. To test this hypothesis, we treated male F344 and SD rats, weighing 180-240 gm with either 0.36 mmol/kg of FeSO4 (Fe+), or equal volumes of saline (Fe-), then placed the animals in >95% oxygen for 48 hours. Mean ± SD. * P<0.05 compared to all other groups. †P<0.05 F344/1.0 Fe+ vs. F344/1.0 Fe-We found that in hyperoxic F-344 rats, both iron-loaded and saline-treated controls, had higher bronchoalveolar lavage protein (BALP) concentrations than did similarly treated air-breathing controls, or hyperoxic SD rats, and that Fe+ hyperoxic F344 rats had higher BALP concentrations and larger pleural effusions than did Fe- hyperoxic F344. Neither group of SD rats exposed to hyperoxia had any significant increase in BAL protein or measurable pleural effusions. These findings support the hypothesis that the increased susceptibility of F344 rats to hyperoxic lung injury may be due to iron-dependent mechanisms. Table

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