Aerosolization of superoxide dismutase. Augmentation of respiratory epithelial lining fluid antioxidant screen by aerosolization of recombinant human Cu++/Zn++ superoxide dismutase. Academic Article uri icon

Overview

MeSH

  • Aerosols
  • Animals
  • Bronchoalveolar Lavage Fluid
  • Epithelium
  • Female
  • Humans
  • Recombinant Proteins
  • Sheep
  • Superoxides

MeSH Major

  • Antioxidants
  • Respiratory System
  • Superoxide Dismutase

abstract

  • 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.

publication date

  • September 1993

has subject area

  • Aerosols
  • Animals
  • Antioxidants
  • Bronchoalveolar Lavage Fluid
  • Epithelium
  • Female
  • Humans
  • Recombinant Proteins
  • Respiratory System
  • Sheep
  • Superoxide Dismutase
  • Superoxides

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 8396002

Additional Document Info

start page

  • 811

end page

  • 815

volume

  • 104

number

  • 3