A Free Radical Scavenger (Lazaroid U75412E) Attenuates Tumor Necrosis Factor-Alpha Generation in a Rabbit Model of Smoke-Induced Lung Injury

  • Shengjun Wang
  • , R. Clark Lantz
  • , Evelyn D. Rider
  • , Guan Jie Chen
  • , Veronica Breceda
  • , Allison M. Hays
  • , Raymond F. Robledo
  • , Brian J. Tollinger
  • , S. V.R. Dinesh
  • , Mark L. Witten

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The lazaroid (21-aminosteroid) analogue U75412E was evaluated in rabbits exposed to diesel fuel-polycarbonate plastic smoke. Inhalation of a total of 4.6 mg U75412E aerosolized at a rate of 1.53 mg/min for 3 min before or after smoke significantly prevented or limited the extent of alveolar hypoventilation, interstitial edema, and tumor necrosis factor-α (TNF-α) by pulmonary alveolar macrophages (PAM) ex vivo observed at 2 h. The smoke-induced changes in wet lung/body weight ratios and the production of superoxide (O2 by PAM ex vivo were also attenuated by the drug treatment after smoke exposure (p ¼ 0.05). This study suggests that lazaroids may ameliorate the oxygen-radical-initiated cytokine processes and inflammation cascade as a result of the smoke insult.

Original languageEnglish (US)
Pages (from-to)358-363
Number of pages6
JournalRespiration
Volume64
Issue number5
DOIs
StatePublished - Jan 1 1997
Externally publishedYes

Keywords

  • Acute lung injury
  • Lazaroid
  • Pulmonary alveolar macrophages
  • Smoke
  • Superoxide
  • Tumor necrosis factor-andα

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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