The effects of melatonin, a free-radical scavenger and a general antioxidant, on radiation-induced growth plate injury have not been studied previously. The purpose of this study was to determine the potential benefits of sparing longitudinal bone growth by fractionated radiotherapy alone compared with pretreatment with melatonin that provides differential radioprotection of normal cells. Weanling 4-wk-old (75-100 g) male Sprague-Dawley rats were randomly assigned to one of three groups: Group R received fractionated radiation alone (n = 8); groups M5 (n = 8) and M15 (n = 7) received 5 or 15 mg/kg melatonin prior to fractionated radiation, respectively. The distal femur and proximal tibia in the right leg of each animal were exposed to a therapeutic X-irradiation dose (25 Gy total in three fractions) with the contralateral left leg as the non-irradiated control. Melatonin was administered intraperitoneally to the animals 30 min before radiation exposure. Six weeks after treatment, the rats were killed and the lower limbs disarticulated, skeletonized, radiographed, and bone growth was calculated based on measurement of the bone lengths. Fractionated radiation resulted in a mean percent overall limb growth loss of 41.2 +/- 9.5 and a mean percent overall limb discrepancy of 11.2 +/- 2.2. The administration of 5 or 15 mg/kg melatonin before each of the three fractions of radiotherapy reduced the mean percent overall limb growth loss to 33.9 +/- 5.8 and 32.2 +/- 4.5, respectively, and the mean percent overall limb discrepancy to 9.4 +/- 1.6 and 8.9 +/- 1.1, respectively; these values were significantly different compared with irradiation alone (range: P = 0.01-0.04). When compared with Group R, the growth arrest recovered by 5 or 15 mg/kg melatonin was 19.7 and 24.1% for the tibia, 7 and 18.6% for the femur, and 17.7 and 21.8% for the total limb, respectively. These results support further investigation of melatonin in combination with fractionation for potential use in growing children requiring radiotherapy to the extremity for malignant tumors.

中文翻译：

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褪黑素对断奶大鼠模型中辐射诱导的骨epi损伤的保护作用。

褪黑激素，一种自由基清除剂和一种普通的抗氧化剂对辐射诱发的生长板损伤的影响以前尚未研究过。这项研究的目的是确定单独的分段放疗与采用褪黑素预处理（提供正常细胞的差异放射防护）相比，保留纵向骨生长的潜在益处。将断奶的4周龄（75-100 g）雄性Sprague-Dawley大鼠随机分为三组之一：R组仅接受分级放射（n = 8）； R组仅接受分级放射。M5组（n = 8）和M15（n = 7）在分次辐射前分别接受5或15 mg / kg褪黑激素。将每只动物右腿的股骨远端和胫骨近端暴露于治疗性X射线辐射剂量（共25 Gy，分为三部分），对侧左腿作为非辐射对照。在辐射暴露前30分钟向动物腹膜内施用褪黑激素。治疗六周后，将大鼠处死，下肢关节脱臼，骨骼化，X线摄影，并根据骨长的测量值计算骨的生长。分级辐射导致肢体总体生长损失的平均百分比为41.2 +/- 9.5，肢体总体差异的平均百分比为11.2 +/- 2.2。在放射治疗的三个部分中的每一个部分之前，分别服用5或15 mg / kg褪黑激素可使整体肢体生长损失的平均百分比分别降低至33.9 +/- 5.8和32.2 +/- 4.5。平均总肢体差异百分比分别为9.4 +/- 1.6和8.9 +/- 1.1；这些值与单独照射相比有显着差异（范围：P = 0.01-0.04）。与R组比较，以5或15 mg / kg褪黑素恢复的生长停滞，胫骨分别为19.7％和24.1％，股骨分别为7和18.6％，全肢分别为17.7和21.8％。这些结果支持褪黑激素与分级分离的进一步研究，以用于可能需要放射疗法治疗恶性肿瘤的成长中的儿童。胫骨分别为1％，股骨分别为7和18.6％，全肢分别为17.7和21.8％。这些结果支持褪黑激素与分级分离的进一步研究，以用于可能需要放射疗法治疗恶性肿瘤的成长中的儿童。胫骨分别为1％，股骨分别为7和18.6％，全肢分别为17.7和21.8％。这些结果支持褪黑激素与分级分离的进一步研究，以用于可能需要放射疗法治疗恶性肿瘤的成长中的儿童。