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

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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

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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    Wang, S., Lantz, R. C., Rider, E. D., Chen, G. J., Breceda, V., Hays, A. M., Robledo, R. F., Tollinger, B. J., Dinesh, S. V. R., & Witten, M. L. (1997). A Free Radical Scavenger (Lazaroid U75412E) Attenuates Tumor Necrosis Factor-Alpha Generation in a Rabbit Model of Smoke-Induced Lung Injury. Respiration, 64(5), 358-363. https://doi.org/10.1159/000196704