Protective effect of melatonin against fractionated irradiation-induced epiphyseal injury in a weanling rat model

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Published on Tuesday, 05 March 2019

Abstract

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.

 

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See also:

- Official Web Site: The Di Bella Method;

- The Di Bella Method (A Fixed Part - Melatonin tablets. From 30-40mg/day up to 200mg/day orally in patients with advanced stage of cancer disease and/or patients without respond to traditional treatments);

- Melatonin with adenosine solubilized in water and stabilized with glycine for oncological treatment - technical preparation, effectivity and clinical findings;

- About Melatonin - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - Calcium, 2 grams per day, orally);

- Vitamin D (analogues and/or derivatives) and cancer - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - Dihydrotachysterol, Alfacalcidol, synthetic Vitamin D3);

- The Di Bella Method (A Fixed Part - Alpha tocopheryl acetate/Vitamin E, approximately 20 grams per day orally);

- Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy;

- All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives) - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - All-Trans Retinoic Acid, Analogues and/or Derivatives - Approximately 60mg per day orally: 40mg per day Beta-Carotene/β-Carotene, 10mg per day ATRA and 10mg per day Axerophthol palmitate);

- The Di Bella Method (A Fixed Part - Vitamin C/Ascorbic Acid, 2–4 grams, twice a day orally);

- Beta-Carotene or β-carotene in Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy;

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- Complete objective response to biological therapy of plurifocal breast carcinoma;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Chronic Lymphocytic Leukemia: Long-Lasting Remission with Combination of Cyclophosphamide, Somatostatin, Bromocriptine, Retinoids, Melatonin, and ACTH;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

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