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Acta Physiologica 2012; Volume 206, Supplement 693
Joint FEPS and Spanish Physiological Society Scientific Congress 2012
9/8/2012-9/11/2012
Santiago de Compostela, Spain
BENEFICIAL EFFECTS OF TOPIC MELATONIN ADMINISTRATION AGAINST MITOCHONDRIAL DAMAGE DURING RADIOTHERAPY-INDUCED MUCOSITIS
Abstract number: P45
Ortiz1 FJ, Dayoub1 JC, Bullejos1 J, Lopez1 A, Doerrier1 C, Venegas1 C, Leonardo-Mendoza1 R, Garcia-Corzo1 L, Luna-Sanchez1 M, Volt1 H, Lopez1 LC, Acuna-Castroviejo1 D, Escames1 G
1Instituto de Biotecnologa, Universidad de Granada
Objectives:
This study was designed to evaluate the existence of mitochondrial damage that may underlie the pathophysiology of the radiotherapy-induced oral mucositis. The objectives of this study were: 1) to analyze the mitochondrial damage following radiotherapy-induced oxidative stress and inflammation, and 2) to evaluate whether the reduction of mitochondrial dysfunction by local application of a new pharmaceutical formulation of melatonin.
Materials:
Male Wistar rats were subjected to irradiation with a X-Ray YXLON Y.Tu 320-D03 irradiator, and the animals received a dose of 7,5 Gy/day for 5 days in their tongues. Rats were treated with 45 mg/day melatonin or vehicle during 21 days post-irradiation, either by local application into their mouths (melatonin gel) or by sc injection. After treatments, rat tongues were obtained for the subsequent determinations.
Results:
A typical irradiation-induced oral mucositis was macroscopically observed, which was absolutely prevented by local melatonin gel treatment. Electron microscopy also showed tongue's mitochondria significantly damaged and broken after radiotherapy, which was also prevented by local melatonin gel administration. Mitochondrial respiration and bioenergetics were significantly impaired by radiotherapy, whereas local melatonin restored mitochondrial function and ATP production, increasing the activity of the mitochondrial antioxidant enzymes. These effects were much more significant with local gel application of melatonin than after its systemic.
Conclusions:
Mitochondrial impairment is an important pathophysiological event during radiotherapy-induced oral mucositis. A new pharmaceutical formulation of melatonin in gel provided an excellent drug therapy in preventing the development of oral mucositis. Considering the low toxicity of melatonin even at high doses and during long term treatments, our results support strong evidence for the therapeutic value of melatonin to prevent mucositis in radiotherapy-treated cancer patients.
To cite this abstract, please use the following information:
Acta Physiologica 2012; Volume 206, Supplement 693 :P45