Melatonin protects rats from radiotherapy-induced small intestine toxicity Fernández-Gil, Beatriz Moneim, Ahmed E. Abdel Ortiz García, Francisco José Shen, Ying-Qiang Soto-Mercado, Viviana Mendivil-Pérez, Miguel Guerra Librero Rite, Ana Acuña Castroviejo, Darío Molina-Navarro, María M. García-Verdugo, José M. Sayed, Ramy K. A. Florido Ruiz, Javier Luna, Juan D. López, Luis Carlos Escames Rosa, Germaine Melatonin Small intestine Mitochondria Gastrointestinal tract Cancer treatment Toxicity Tongue Radiation therapy Radiotherapy-induced gut toxicity is among the most prevalent dose-limiting toxicities following radiotherapy. Prevention of radiation enteropathy requires protection of the small intestine. However, despite the prevalence and burden of this pathology, there are currently no effective treatments for radiotherapy-induced gut toxicity, and this pathology remains unclear. The present study aimed to investigate the changes induced in the rat small intestine after external irradiation of the tongue, and to explore the potential radio-protective effects of melatonin gel. Male Wistar rats were subjected to irradiation of their tongues with an X-Ray YXLON Y.Tu 320-D03 irradiator, receiving a dose of 7.5 Gy/day for 5 days. For 21 days post-irradiation, rats were treated with 45 mg/day melatonin gel or vehicle, by local application into their mouths. Our results showed that mitochondrial oxidative stress, bioenergetic impairment, and subsequent NLRP3 inflammasome activation were involved in the development of radiotherapy-induced gut toxicity. Oral treatment with melatonin gel had a protective effect in the small intestine, which was associated with mitochondrial protection and, consequently, with a reduced inflammatory response, blunting the NF-κB/NLRP3 inflammasome signaling activation. Thus, rats treated with melatonin gel showed reduced intestinal apoptosis, relieving mucosal dysfunction and facilitating intestinal mucosa recovery. Our findings suggest that oral treatment with melatonin gel may be a potential preventive therapy for radiotherapy-induced gut toxicity in cancer patients. 2017-05-10T10:23:07Z 2017-05-10T10:23:07Z 2017-04-12 info:eu-repo/semantics/article Fernández-Gil, B.; et al. Melatonin protects rats from radiotherapy-induced small intestine toxicity. Plos One, 12(4): e0174474 (2017). [http://hdl.handle.net/10481/46291] 1932-6203 http://hdl.handle.net/10481/46291 10.1371/journal.pone.0174474 eng http://creativecommons.org/licenses/by-nc-nd/3.0/ info:eu-repo/semantics/openAccess Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License Public Library of Science (PLOS)