Pulmonary oxygen toxicity in mice is characterized by alterations
in ascorbate redox status.
Rusakow, Lee S., Jihong Han, Mike A. Hayward, and Owen W. Griffith.
Departments of Pediatrics and Biochemistry, Medical College of
Wisconsin, Milwaukee, WI 53226
APStracts 2:0292A, 1995.
Pulmonary oxygen toxicity results from disruption of the body's usual
antioxidant defenses. We therefore investigated whether mice
suffering from oxygen toxicity show significant alterations in the
redox status of ascorbate, an important antioxidant, as reflected by
changes in the relative amounts of its oxidized and reduced forms.
Mice were exposed to air or hyperoxia (>97% O2, 760 mmHg). After
5 days, plasma and saline-perfused lungs were removed, and levels of
ascorbate (AA), oxidized ascorbate (dehydroascorbate; DHAA) and total
ascorbate species ([AA+DHAA]) were determined by a sensitive and
specific HPLC assay; lungs were also assayed for total 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/[AA+DHAA] ratio increased. In contrast, in lung,
[AA+DHAA] decreased by 41%. Plasma AA, DHAA, and [AA+DHAA] each
correlated inversely with lung [AA+DHAA] and directly with lung GSSG.
We conclude that alterations in plasma ascorbate redox status reflect
pulmonary oxygen toxicity in mice. Our results suggest that further
investigations to determine whether similar findings occur in humans
and have clinical utility are warranted.
Received 14 December 1994; accepted in final form 14 June 1995.
APS Manuscript Number A1272-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 11 July 1995.