376. Int J Radiat Oncol Biol Phys. 1996 Jan 1;34(1):111-5.
Effect of high-dose pentoxifylline on acute radiation-induced lung toxicity in a
rat lung perfusion model.
Stelzer KJ(1), Koh WJ, Peterson LM, Griffin TW.
Author information:
(1)Department of Radiation Oncology, University of Washington Medical Center,
Seattle 98195, USA.
PURPOSE: 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 AND MATERIALS: 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.
PMID: 12118538 [PubMed - indexed for MEDLINE]