PULMONARY OXYGEN-TOXICITY IN MICE IS CHARACTERIZED BY ALTERATIONS IN ASCORBATE REDOX STATUS

Pulmonary oxygen toxicity results from disruption of the usual antioxi dant defenses of the body. We therefore investigated whether mice that suffer from oxygen toxicity show significant alterations in the redox status of ascorbate, an important antioxidant, as reflected by change s in the relative amounts of its oxidized and reduced forms. Mice were exposed to air or hyperoxia (>97% O-2, 760 mmHg). After 5 days, plasm a and saline-perfused lungs were removed and levels of ascorbate (AA), oxidized ascorbate [dehydroascorbate (DHAA)], and total ascorbate spe cies ([AA + DHAA]) were determined by a sensitive and specific high-pe rformance liquid chromatography assay; lungs were also assayed for tot al glutathione and glutathione disulfide (GSSG), an established marker of oxidative stress. We found that with hyperoxic exposure plasma AA increased by 32%, plasma DHAA increased substantially from previously undetectable levels, and the DHAA-to-[AA+DHAA] ratio increased. In con trast, in lung, [AA+DHAA] decreased by 41%. Plasma AA, DHAA, and [AA+D HAA] each correlated inversely with lung [AA + DHAA] and directly with lung GSSG. We conclude that alterations in plasma ascorbate redox sta tus reflect pulmonary oxygen toxicity in mice. Our results suggest tha t further investigations are warranted to determine whether similar fi ndings occur in humans and have clinical utility.