International Journal of Medical Sciences

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24 September 2017

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Int J Med Sci 2017; 14(11):1065-1071. doi:10.7150/ijms.20245

Research Paper

Effects Of Oral Glutamine on Inflammatory and Autophagy Responses in Cancer Patients Treated With Abdominal Radiotherapy: A Pilot Randomized Trial

Juan J. Ortiz de Urbina1, 3, Beatriz San-Miguel1, Alfonso Vidal-Casariego4, Irene Crespo1, 2, Diana I. Sánchez1, José L. Mauriz1, 2, Jesús M. Culebras1, Javier González-Gallego1, 2, María J. Tuñón1, 2✉

1. Institute of Biomedicine (IBIOMED), University of León, León, Spain;
2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain;
3. Pharmacy Service, Complejo Asistencial Universitario de León, León, Spain;
4. Endocrinology and Nutrition Service, Complejo Asistencial Universitario de León, León, Spain.

Abstract

Background and Aims: Abdominal radiotherapy (RT) causes harm to the mid gastrointestinal mucosa by release of pro-inflammatory cytokines and promotes autophagic changes in tumor cells. This study was aimed to measure the effect of glutamine administration on markers of inflammation and autophagy in cancer patients treated with RT.

Methods: In this double-blind, randomized, controlled pilot trial 43 patients under abdominal RT diagnosed of pelvic or abdominal malignancies receiving glutamine (30 g/d) or placebo (casein, 30 g/d). Patient recruitment took place in the Complejo Asistencial Universitario of León (CAULE), Spain. Patient evaluation took place at three different time points during the study: before RT (pre-treatment), in the middle of the RT period (mid-treatment), and after finishing RT (post-treatment). Data were compared by analysis of variance and the Newmann Keuls test. Significance was accepted at p < 0.05.

Results Abdominal RT increased whole blood mRNA levels of inflammatory and autophagic markers, but glutamine administration showed significantly lower expression of toll-like receptor 4 (TLR4), CD36, interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), and matrix metalloproteinase-9 (MMP-9). Moreover, glutamine reduced the expression of the transcription factors nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1). Glutamine also inhibited the autophagic response, with changes in expression of beclin-1, UV radiation resistance associated gene (UVRAG), autophagy-related protein-5 (Atg5), protein 1 light chain 3 (LC3), sequestosome 1 (p62/SQSTM1) and lysosome-associated membrane protein (LAMP)-1.

Conclusions Findings provide evidence that glutamine decreases the inflammatory response and abolishes the changes of the autophagy machinery in patients receiving abdominal RT. The protective effect of glutamine must continue being investigated to disclose further molecular pathways.

Keywords: glutamine, clinical trial, inflammation, autophagy, radiotherapy.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
de Urbina JJO, San-Miguel B, Vidal-Casariego A, Crespo I, Sánchez DI, Mauriz JL, Culebras JM, González-Gallego J, Tuñón MJ. Effects Of Oral Glutamine on Inflammatory and Autophagy Responses in Cancer Patients Treated With Abdominal Radiotherapy: A Pilot Randomized Trial. Int J Med Sci 2017; 14(11):1065-1071. doi:10.7150/ijms.20245. Available from http://www.medsci.org/v14p1065.htm