title: Effect of pentoxifylline on radiation-induced lung and skin toxicity in rats.
abstract: OBJECTIVE
  There is currently substantial clinical interest in pentoxifylline as an inhibitor of radiation-related normal tissue injury. To further assess this drug's potential toxicity-sparing effects, pentoxifylline was studied in rats using a radiation-induced lung injury model.
  
  
  METHODS
  Adult male rats were exposed to either sham irradiation or a single fraction of 21 Gy delivered to the left hemithorax. Four study groups were defined: those that received neither radiation nor pentoxifylline, those that received pentoxifylline (500 mg/L in drinking water) but no irradiation, those that underwent irradiation without pentoxifylline, and those that received both pentoxifylline and radiation. Lung injury was measured by changes in relative left:right lung perfusion ratios derived from quantitative gamma camera imaging of 99mTechnetium-macroaggregated albumin uptake in the pulmonary circulation. Serial scans were done over a 40-week period following radiation. Skin toxicity was also assessed. After 40 weeks, the animals were killed, and lung tissue was assayed for angiotensin converting enzyme activity as a marker for endothelial cell damage.
  
  
  RESULTS
  Both groups of radiated (with or without pentoxifylline) rats showed equivalent acute sharp decreases in left:right lung perfusion ratios compared to the nonirradiated groups, reaching a mean nadir value of 0.29 at week 4. Irradiated lung perfusion in subsequent weeks in the radiation-only group showed minimal recovery, with a plateau mean ratio of 0.37 (0.36-0.39). However, there was apparent later recovery of lung perfusion in the radiation with pentoxifylline group from weeks 14 through 40, to a mean ratio of 0.47 (0.43-0.52) (p < 0.01 compared to the radiation-only group). Angiotensin converting enzyme activity correlated closely with lung perfusion data. No effect of pentoxifylline on acute or late skin toxicity was detected.
  
  
  CONCLUSIONS
  This study suggests that pentoxifylline does not have any measurable effect on acute lung injury following hemithoracic irradiation in rats, but does result in sparing of later lung toxicity.
authors.affiliation: Department of Radiation Oncology, University of Washington Medical Center, Seattle 98195.
authors.forename: W J
authors.initials: WJ
authors.lastname: Koh
authors.forename: K J
authors.initials: KJ
authors.lastname: Stelzer
authors.forename: L M
authors.initials: LM
authors.lastname: Peterson
authors.forename: B L
authors.initials: BL
authors.lastname: Staker
authors.forename: W F
authors.initials: WF
authors.lastname: Ward
authors.forename: K J
authors.initials: KJ
authors.lastname: Russell
authors.forename: T W
authors.initials: TW
authors.lastname: Griffin
mesh_terms: D000818:Animals; D008168:Lung / Q000201:enzymology / Q000528:radiation effects*; D008297:Male; D010431:Pentoxifylline / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011652:Pulmonary Circulation / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000528:radiation effects
chemical_list: D007703:Peptidyl-Dipeptidase A; D010431:Pentoxifylline