Aerosolization of superoxide dismutase: Augmentation of respiratory epithelial lining fluid antioxidant screen by aerosolization of recombinant human Cu++/Zn++ superoxide dismutase

A. Gillissen, J. H. Roum, R. F. Hoyt, Ronald Crystal

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 μmol/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.

Original languageEnglish
Pages (from-to)811-815
Number of pages5
JournalChest
Volume104
Issue number3
Publication statusPublished - 1 Jan 1993
Externally publishedYes

Fingerprint

Superoxide Dismutase
Antioxidants
Aerosols
Lung Diseases
Sheep
Superoxide Dismutase-1
Oxidants
Anions
Phosphates
Lung
Therapeutics
Proteins

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Aerosolization of superoxide dismutase : Augmentation of respiratory epithelial lining fluid antioxidant screen by aerosolization of recombinant human Cu++/Zn++ superoxide dismutase. / Gillissen, A.; Roum, J. H.; Hoyt, R. F.; Crystal, Ronald.

In: Chest, Vol. 104, No. 3, 01.01.1993, p. 811-815.

Research output: Contribution to journalArticle

@article{690c84c252cf49f6a6176d4469022bc7,
title = "Aerosolization of superoxide dismutase: Augmentation of respiratory epithelial lining fluid antioxidant screen by aerosolization of recombinant human Cu++/Zn++ 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 μmol/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.",
author = "A. Gillissen and Roum, {J. H.} and Hoyt, {R. F.} and Ronald Crystal",
year = "1993",
month = "1",
day = "1",
language = "English",
volume = "104",
pages = "811--815",
journal = "Chest",
issn = "0012-3692",
publisher = "American College of Chest Physicians",
number = "3",

}

TY - JOUR

T1 - Aerosolization of superoxide dismutase

T2 - Augmentation of respiratory epithelial lining fluid antioxidant screen by aerosolization of recombinant human Cu++/Zn++ superoxide dismutase

AU - Gillissen, A.

AU - Roum, J. H.

AU - Hoyt, R. F.

AU - Crystal, Ronald

PY - 1993/1/1

Y1 - 1993/1/1

N2 - 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 μmol/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.

AB - 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 μmol/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.

UR - http://www.scopus.com/inward/record.url?scp=0027227895&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027227895&partnerID=8YFLogxK

M3 - Article

C2 - 8396002

AN - SCOPUS:0027227895

VL - 104

SP - 811

EP - 815

JO - Chest

JF - Chest

SN - 0012-3692

IS - 3

ER -