Aerosolization of superoxide dismutase. Augmentation of respiratory epithelial lining fluid antioxidant screen by aerosolization of recombinant human Cu++/Zn++ superoxide dismutase
Various human pulmonary diseases are characterized by an increased oxidant burden on the respiratory epithelial surface. As a step toward developing a therapy to augment the antioxidant defenses of respiratory epithelial lining fluid (ELF) of the human lung, we have evaluated the feasibility of aero...
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Veröffentlicht in: | Chest 1993-09, Vol.104 (3), p.811-815 |
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Zusammenfassung: | Various human pulmonary diseases are characterized by an increased oxidant burden on the respiratory epithelial surface. As
a step toward developing a therapy to augment the antioxidant defenses of respiratory epithelial lining fluid (ELF) of the
human lung, we have evaluated the feasibility of aerosolizing a human protein antioxidant to the respiratory epithelial surface
of an experimental animal sufficiently large to permit repetitive sampling of ELF. To accomplish this, recombinant human Cu++/Zn++
superoxide dismutase (rSOD) was aerosolized to sheep, and the levels of human superoxide dismutase (SOD) and antisuperoxide
anion (O2.-) capacity were quantified in ELF over time. In vitro aerosolization did not alter the specific activity of rSOD
(p > 0.5). In vivo aerosolization of rSOD (100 mg) to sheep (n = 7) resulted in peak amounts of human Cu++/Zn++ SOD in ELF
of 3.1 +/- 0.6 mumol/L, with a parallel increase in the anti-O2.- capacity of ELF. For the duration of the study (5 h), levels
of SOD and anti-O2.- in ELF remained elevated, with a value 50 percent of the peak at 5 h. Aerosolization of phosphate-buffered
saline (n = 5) had no effect on SOD or anti-O2.- levels in ELF. In animals receiving rSOD, there was no change in the specific
activity of SOD recovered in ELF compared to the starting material (p > 0.4). We conclude that rSOD can be delivered by aerosol
to the ELF of a large animal with preservation of specific activity and that a substantial increase in both the amount of
SOD and the anti-O2.- capacity can be achieved for a period of time applicable to human therapy, supporting the rationale
for evaluation of rSOD aerosol as an antioxidant in human pulmonary disease. |
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ISSN: | 0012-3692 1931-3543 |
DOI: | 10.1378/chest.104.3.811 |