Attenuation of oxidant-induced lung injury by 21-aminosteroids (lazaroids): correlation with the mRNA expression for E-selectin, P-selectin, ICAM-1, and VCAM-1. Environ Health Perspect 1994 Dec;102 Suppl 10(Suppl 10):193-200
Date
12/01/1994Pubmed ID
7535686Pubmed Central ID
PMC1567004DOI
10.1289/ehp.94102s10193Scopus ID
2-s2.0-0028575737 (requires institutional sign-in at Scopus site) 25 CitationsAbstract
We compared the effects of treatment with methylprednisolone or the 21-aminosteroids, U-74389 and U-74006F (Tirilizad mesylate), on hyperoxic lung injury and the associated expression of mRNA for several adhesion molecules in rats. Inhalation of > 95% oxygen for up to 72 hr in Sprague-Dawley rats produced a marked increase in lung weight and an accumulation of fluid in the thorax when compared with air-breathing controls. Hyperoxia also induced a marked neutrophil-rich influx of inflammatory cells into the bronchial lumen as measured by bronchoalveolar lavage. Neutrophil numbers in bronchoalveolar lavage fluid peaked after 60 hr of exposure to s 95% oxygen; this was associated with a marked upregulation of mRNA for the adhesion molecules P-selectin and E-selectin but not VCAM-1. mRNA for ICAM-1 was constitutively expressed at high levels in both air-breathing controls and in the lungs of rats exposed to high concentrations of oxygen. Pretreatment with the 21-aminosteroids reduced hyperoxic lung damage and improved survival times in animals exposed to > 95% oxygen. However, treatment with methylprednisolone significantly decreased survival times. Treatment with U-74389 did not significantly (p > 0.05) inhibit the BAL neutrophilia and did not significantly (p > 0.05) reduce hyperoxia-induced increases in mRNA expression for P-selectin and E-selectin. The inhibition of hyperoxic lung damage coupled with improved survival seen in treated animals suggests that 21-aminosteroids may provide valuable treatments for pulmonary disorders in which oxidant damage has been implicated.
Author List
Griffin RL, Krzesicki RF, Fidler SF, Rosenbloom CL, Auchampach JA, Manning AM, Haas JV, Cammarata SK, Chin JE, Richards IMAuthor
John A. Auchampach PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntioxidants
Cell Adhesion Molecules
E-Selectin
Free Radical Scavengers
Intercellular Adhesion Molecule-1
Lung
Lung Diseases
Male
Methylprednisolone
Neutrophils
Oxidants
P-Selectin
Platelet Membrane Glycoproteins
Pregnatrienes
RNA, Messenger
Rats
Rats, Sprague-Dawley
Vascular Cell Adhesion Molecule-1
