A free radical scavenger (Lazaroid U75412E) attenuates tumor necrosis factor-alpha generation in a rabbit model of smoke-induced lung injury.
The lazaroid (21-aminosteroid) analogue U75412E was evaluated in rabbits exposed to diesel fuel-polycarbonate plastic smoke. Inhalation of 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-alpha (TNF-alpha) 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 < 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.
Wang
S
S
Department of Pediatrics, Joan B. and Donald R. Diamond Lung Injury Laboratories of the Steele Memorial Children's Research Center, Tucson, Ariz, USA.
Lantz
R C
RC
Rider
E D
ED
Chen
G J
GJ
Breceda
V
V
Hays
A M
AM
Robledo
R F
RF
Tollinger
B J
BJ
Dinesh
S V
SV
Witten
M L
ML
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001681:Biological Assay; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects*; D009336:Necrosis; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011817:Rabbits; D015208:Smoke Inhalation Injury / Q000517:prevention & control*; D013256:Steroids / Q000008:administration & dosage / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000187:drug effects*
D000975:Antioxidants; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha; C069980:U 75412E