Aerosolized manganese SOD decreases hyperoxic pulmonary injury in primates. II. Morphometric analysis.

Published

Journal Article

Hyperoxia damages lung parenchyma via increased cellular production of reactive oxygen species that exceeds antioxidant defenses. We hypothesized that aerosolized human recombinant manganese superoxide dismutase (rhMnSOD) would augment extracellular antioxidant defenses and attenuate epithelial injury in the lung during hyperoxia in primates. Twenty-four adult male baboons were anesthetized and mechanically ventilated with 100% oxygen for 96 h. The baboons were divided equally into four groups. Oxygen alone and oxygen plus rhMnSOD given at 3 mg . kg-1 . day-1 were compared to assess efficacy of the drug. Subsequently, aerosolized rhMnSOD was given at 1 or 10 mg . kg-1 . day-1 to study dose effects and toxicity. Quantitative morphometry showed protection of alveolar epithelium from hyperoxia by 3 mg . kg-1 . day-1 rhMnSOD (P < 0.05). In addition, interstitial fibroblast volumes were increased in the treatment group (P = 0.06). This effect appeared greater at the two higher doses of the rhMnSOD. The aerosolized drug was localized to the surface of airways and air spaces and macrophages by immunolabeling studies, suggesting efficacy via physicochemical properties that localize it to cell surfaces or by effects on alveolar macrophage function.

Full Text

Duke Authors

Cited Authors

  • Welty-Wolf, KE; Simonson, SG; Huang, YC; Kantrow, SP; Carraway, MS; Chang, LY; Crapo, JD; Piantadosi, CA

Published Date

  • August 1997

Published In

Volume / Issue

  • 83 / 2

Start / End Page

  • 559 - 568

PubMed ID

  • 9262453

Pubmed Central ID

  • 9262453

International Standard Serial Number (ISSN)

  • 8750-7587

Digital Object Identifier (DOI)

  • 10.1152/jappl.1997.83.2.559

Language

  • eng

Conference Location

  • United States