misoprostol and Leg-Length-Inequality

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.. 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.. 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.. 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.

Topics: Animals; Bone Development; Bone Regeneration; Interleukin-1; Leg Bones; Leg Length Inequality; Male; Misoprostol; Models, Animal; Pentoxifylline; Radiation Injuries, Experimental; Radiation-Protective Agents; Rats; Rats, Sprague-Dawley; Selenium

Radiotherapy used in the treatment of bone and soft tissue sarcomas in pediatric patients often results in undesirable growth plate damage. Radioprotectants may hold promise in the selective protection of growth plate tissue in this setting. In an animal model, the hypothesis tested was that pentoxifylline, selenium, or misoprostol, used in combination with amifostine, would significantly reduce longitudinal growth loss during one radiation dose exposure to a greater extent than the protection provided by only amifostine without increased morbidity or mortality or adverse effects on bone mineral density. Amifostine alone and in combination with each of the other radioprotectants resulted in limb discrepancy reduction to levels significantly less than radiated controls. The tibial length discrepancy in the selenium and amifostine group was 12.1 +/- 0.8%, less than the 15.5 +/- 2.6% tibial length discrepancy in the animals treated with amifostine alone, and less than the mean 18.8% tibial length discrepancy in the radiated limbs without radioprotection. There were no adverse effects on bone density in any group, but the selenium and amifostine group showed some increased mortality. Combinations of amifostine with these radioprotectants show efficacy in growth plate radioprotection and therefore warrant additional study in a clinically relevant fractionated model.

Topics: Amifostine; Animals; Body Weight; Bone Density; Bone Development; Drug Therapy, Combination; Femur; Growth Plate; Leg Length Inequality; Male; Misoprostol; Pentoxifylline; Radiation Dosage; Radiation Injuries, Experimental; Radiation-Protective Agents; Rats; Rats, Sprague-Dawley; Selenium; Tibia