Pentoxifylline does not protect against hyperoxic lung injury in rats.
Hyperoxia has been used extensively as a model of acute lung injury. The drug pentoxifylline has been shown to have a protective effect in other models of lung injury. We sought to determine whether pentoxifylline protects against hyperoxic lung injury in rats by decreasing the accumulation of neutrophils within the lung. A total of 84 rats were studied. Twenty four rats were randomized into four groups. Two groups of rats were pretreated for 48 h with either pentoxifylline (20 mg.kg-1) or saline, and then exposed to > 95% O2 for 60 h while treatments continued. Two groups of control rats received the same treatment regimens as the O2-exposed animals, but breathed room air. Neutrophil accumulation in the lung was quantified both by histology and myeloperoxidase activity. Lung neutrophil accumulation increased in the oxygen-exposed group receiving pentoxifylline as compared to oxygen- or air-exposed rats receiving saline injections. Total glutathione was higher in lung homogenates from the hyperoxic, pentoxifylline-treated group than in homogenates from the other three groups. To study survival, 60 rats were exposed to > 95% O2 for 120 h, 30 rats were pretreated with pentoxifylline, and 30 received saline. Survival after 120 h of exposure to hyperoxia was not altered by pentoxifylline treatment (pentoxifylline treated: 6 out of 30 survived; saline treated: 2 out of 30 survived). We conclude that pentoxifylline does not reduce mortality or lung injury in rats exposed to hyperoxia and is associated with an increase in lung neutrophil accumulation.
Section of Pulmonary and Critical Care Medicine, Michael Reese Hospital, University of Illinois Hospital at Chicago 60616.
E T
ET
Naureckas
P
P
Factor
O
O
Benjaminov
E
E
Hoffer
V
V
Sriram
J I
JI
Sznajder
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D018496:Hyperoxia / Q000150:complications*; D008168:Lung / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000473:pathology / Q000502:physiology; D010431:Pentoxifylline / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*
D010431:Pentoxifylline