Early alterations of lung injury following acute smoke exposure and 21-aminosteroid treatment.
In a simulated fire-related smoke exposure protocol, New Zealand white rabbits were utilized to investigate the potential effects of the 21-aminosteroid (lazaroid) analog U75412E on the early events of acute lung injury. Inhalation of a total of 1.6 mg/kg U75412E aerosolized at a rate of 1.53 mg/min at 0.5 hr after smoke exposure significantly attenuated the extent of lung injury at 1 hr, as evidenced by decreased bronchoalveolar lavage (BAL) concentration of total protein, 6-keto-prostaglandin F1-alpha, and blood gas defect. Histopathologic examination demonstrated that the lazaroid significantly attenuated smoke-induced lung injury as evidenced by a decrease in wet lung/body weight ratio, necrosis, and sloughing of airway epithelial cells. Electron microscopy showed that the lazaroid decreased smoke-induced interstitial edema and the vacuolization of alveolar type II epithelium (21.6 +/- 9.7 vs 8.5 +/- 3.6 vacuoled blebs/cell, smoke only vs smoke + lazaroid). However, U75412E did not attenuate smoke-induced changes in BAL concentration of tumor necrosis factor-alpha, total cell count, and granulocyte percentage. These observations suggest that U75412E may exert its action through cooperative mechanisms, such as the modulation of arachidonic acid metabolism, in addition to its characterized antioxidative effects.
Wang
S
S
Department of Pediatrics, University of Arizona, Tucson 85724, USA.
Lantz
R C
RC
Robledo
R F
RF
Breceda
V
V
Hays
A M
AM
Witten
M L
ML
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001784:Blood Gas Analysis; D001980:Bronchi / Q000187:drug effects / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D004847:Epithelial Cells / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008171:Lung Diseases / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D009929:Organ Size / Q000187:drug effects; D011506:Proteins / Q000032:analysis; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D011817:Rabbits; D012906:Smoke / Q000009:adverse effects*; D015208:Smoke Inhalation Injury / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D013256:Steroids / Q000627:therapeutic use*
D000975:Antioxidants; D011506:Proteins; D012906:Smoke; D013256:Steroids; C069980:U 75412E; D015121:6-Ketoprostaglandin F1 alpha