Methylprednisolone increases the toxicity of oxygen in adult mice. Mechanical and biochemical effects on the surfactant system.
Because previous studies have suggested that some of the toxic effects of oxygen may result from impaired surfactant phospholipid metabolism, we examined the effects of methylprednisolone on the surfactant system in adult mice exposed to greater than 98% O2. Mice pretreated for 7 days with methylprednisolone, 10 mg/kg/day, had a significantly greater mortality in hyperoxia than saline-pretreated, oxygen-exposed control mice. Their bronchoalveolar lavage fluid contained significantly less desaturated phospholipid, and static pressure-volume curves with air and saline showed decreased lung compliance caused by stiffness of the surface layer. The synthesis of desaturated phospholipids by lung slices in vitro was markedly impaired by the first day of hyperoxia, although in the absence of hyperoxia, it was mildly increased. The increased inhibition of phospholipid synthesis in steroid-treated mice was present even when mice were first given steroids on the day of entry into hyperoxia. These results suggest that methylprednisolone has an unfavorable effect on the surfactant system in oxygen toxicity by accentuating the inhibition of phospholipid synthesis. The possibility that these results could have been due to infection promoted by steroid treatment was considered. No cultural, histologic, or serologic evidence in support of this possibility was found, although infection cannot be conclusively excluded.
D000818:Animals; D004357:Drug Synergism; D005260:Female; D008775:Methylprednisolone / Q000633:toxicity*; D051379:Mice; D010100:Oxygen / Q000633:toxicity*; D010743:Phospholipids / Q000096:biosynthesis / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism*; D013718:Tensile Strength
D010743:Phospholipids; D011663:Pulmonary Surfactants; D010100:Oxygen; D008775:Methylprednisolone