Novel radioprotectant drugs for sparing radiation-induced damage to the physis.
OBJECTIVE
To determine if pentoxifylline, interleukin 1alpha, selenium and misoprostol can minimize damage to physeal longitudinal growth during single radiation dose exposure in an animal model.


METHODS
Eighty-seven weanling Sprague-Dawley rats were randomized into 15 drug/dose groups. All groups received a single 17.5-Gy gamma-irradiation exposure to the right knee, the left limb serving as an internal control. Pentoxifylline was injected 30 min before exposure, sodium selenite and interleukin 1alpha 24 h before exposure and misoprostol 2 h before exposure. Positive controls received 17.5 Gy. At 6 weeks, animals were sacrificed, the hind limb lengths were measured and detailed histomorphometric analysis was performed.


RESULTS
Statistically significant reductions (p < or = 0.03) in mean limb length discrepancy compared with irradiation alone were seen following administration of pentoxifylline (50 mg kg(-1)), interleukin 1alpha (15 mcg kg(-1)), selenium (5 mg kg(-1)) and misoprostol (20 mg kg(-1)). Histomorphometric endpoints and growth rate remained altered at 6 weeks despite treatment, but length discrepancy reduction was highly correlated with the appearance of regenerative clones.


CONCLUSIONS
Each drug reduced the amount of anticipated growth arrest in the animal model and some compared favourably in magnitude with that previously demonstrated for the established radioprotectant drug amifostine. Restoration of growth appears related to appearance of regenerative clones.
Damron
T A
TA
Musculoskeletal Research Laboratory, Department of Orthopedic Surgery, Institute for Human Performance at SUNY Upstate Medical University, Syracuse, NY 13210, USA. damront@upstate.edu
Spadaro
J A
JA
Horton
J A
JA
Margulies
B S
BS
Strauss
J A
JA
Farnum
C E
CE
D000818:Animals; D001846:Bone Development / Q000187:drug effects* / Q000528:radiation effects; D001861:Bone Regeneration / Q000187:drug effects / Q000528:radiation effects; D007375:Interleukin-1 / Q000494:pharmacology; D007867:Leg Bones / Q000187:drug effects / Q000528:radiation effects; D007870:Leg Length Inequality / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D016595:Misoprostol / Q000494:pharmacology; D023421:Models, Animal; D010431:Pentoxifylline / Q000494:pharmacology; D011833:Radiation Injuries, Experimental / Q000503:physiopathology; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000494:pharmacology
D007375:Interleukin-1; D011837:Radiation-Protective Agents; D016595:Misoprostol; D012643:Selenium; D010431:Pentoxifylline