Effect of high-dose pentoxifylline on acute radiation-induced lung toxicity in a rat lung perfusion model.
OBJECTIVE
The purpose of this study was to study the effect of high-dose oral pentoxifylline on radiation-induced acute lung injury as assessed with a rat lung perfusion model.


METHODS
Adult male Sprague-Dawley rats were used throughout this study. A preliminary experiment determined that treatment with 2 g/liter pentoxifylline in drinking water resulted in an average consumption of 1.38 g/m2/day, which is comparable to the maximum tolerated dosage in humans. Seventy-two rats were irradiated to the left hemithorax with single fraction doses ranging from 10 through 18 Gy. Half were treated with 2 g/liter pentoxifylline in drinking water from 1 week before radiation through 8 weeks after radiation. Lung vascular perfusion scanning was performed at 3, 4, 5, 6, and 8 weeks after radiation using 99mTc-macroaggregated albumin. The lung perfusion ratio was defined as the number of counts due to radioactivity within the irradiated left lung region of interest divided by the number of counts within the region of the nonirradiated right lung. This lung perfusion ratio has been shown to decrease with radiation-induced lung injury.


RESULTS
Although radiation led to a decreased lung perfusion ratio in all groups, those receiving pentoxifylline maintained higher ratios than irradiated controls from 3-5 weeks, especially for those receiving 15 or 18 Gy. However, from 6 through 8 weeks the irradiated controls exhibited partial recovery of lung perfusion ratio, whereas the pentoxifylline groups did not. By 8 weeks after 15 and 18 Gy, lung perfusion ratios were significantly higher for the irradiated controls than for pentoxifylline-treated rats-a reversal of the pattern observed at 3-5 weeks.


CONCLUSIONS
The protection by pentoxifylline against radiation-induced acute lung injury was transient and limited to the first 5 weeks after radiation. Subsequent recovery from lung injury was inhibited by this drug at later times within the acute phase.
Department of Radiation Oncology, University of Washington Medical Center, Seattle 98195, USA.
K J
KJ
Stelzer
W J
WJ
Koh
L M
LM
Peterson
T W
TW
Griffin
D000208:Acute Disease; D000818:Animals; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000528:radiation effects*; D008297:Male; D010431:Pentoxifylline / Q000008:administration & dosage* / Q000494:pharmacology; D010865:Pilot Projects; D011833:Radiation Injuries, Experimental / Q000188:drug therapy*; D011837:Radiation-Protective Agents / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D011837:Radiation-Protective Agents; D010431:Pentoxifylline