The prophylactic effects of U75412E pretreatment in a smoke-induced lung injury rabbit model

Shengjun Wang, R. Clark Lantz, Guan Jie Chen, Veronica Breceda, Evelyn Rider, Allison M. Hays, Grace Parliman, Brian J. Tollinger, Raymond F. Robledo, Kathleen Kunke, Julieta Tinajero, Mark L. Witten

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


The effects of the lazaroid analogue U75412E (21-[4-(3-ethylamino-2-pyridinyl)-1-piperazinyl]-16α-methylpregna-1,4,9]-(11) -triene-3,2-dione) were examined in an acute lung injury rabbit model. Standard doses of 0, 8 and 16 mM U75412E were aerosolized and ventilated into the lungs for 3 min via an endotracheal tube. A 60 tidal volume dose of diesel fuel-polycarbonate plastic smoke was then instilled, followed by mechanical ventilation for one hour. Pretreatment with 16 mM U75412E significantly increased blood PaO2 and pH values, and decreased blood PaCO2 as compared to smoke only exposures. It also significantly decreased the total cell counts and granulocytes in bronchoalveolar lavage fluid, and the ability of pulmonary alveolar macrophages to produce tumour necrosis factor-α in vitro after cell isolation and culture. Histopathology indicated that 16 mM U75412E pretreatment attenuated increases in wet lung/body weight ratios, inflammatory focus, and interstitial oedema associated with smoke insult. In summary, U75412E pretreatment may possess the potential to improve acute smoke-induced lung injury, in part, through modulation of tumour necrosis factor-α production from pulmonary alveolar macrophages.

Original languageEnglish (US)
Pages (from-to)231-237
Number of pages7
JournalPharmacology and Toxicology
Issue number5
StatePublished - 1996

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis


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