The impact of citicoline on brain injury in rats subjected to head irradiation

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RESEARCH ARTICLE

The impact of citicoline on brain injury in rats subjected to head irradiation Nahed Abdel-Aziz 1 & Enas M. Moustafa 1

&

Helen N. Saada 1

Received: 20 June 2020 / Accepted: 4 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract Hazard and risk associated with the use of radiotherapy play a crucial role in brain injury with interference via the neuroendocrine activity of the cancer survivors, and there is no effective preventive strategy. We conducted this study to assess the effect of citicoline in biosynthesis variants occurring in the cerebral cortex of rats in response to head γ-irradiation. Bio-analysis includes MDA, 8-OHdG, and NO as oxidation indicators; total antioxidant activity; the inflammatory factors TNF-α, IL-1β, and amyloid-β 42 levels; the caspase-3 cell death marker; IGF-I; serum hormones including GH, ACTH, FSH, and LH; and the neurotransmitters acetylcholine, dopamine, and serotonin. We exposed animals to 10 Gy head gamma irradiation followed by citicoline treatment and sustained for 30 days. The animals were sacrificed at the 3rd and 30th day post-irradiation. Citicoline mechanism has been linked to potent radical reduced ability counteracting the oxidative stress–mediated inflammation and apoptosis. Citicoline treatment has normalized the altering recorded in serum hormones associated with a significant modulation in the levels of IGF-1/PI3K/AKT factors. Such improvements have been concomitant with regulated neurotransmitter levels. We could conclude that citicoline may safely be supplemented to avoid both short- and long-term damages to the neuroendocrine disturbances, oxidative stress, inflammation, and apoptosis induced by head irradiation. Keywords Head irradiation . Brain . Citicoline . Neuroendocrine . IGF-1/PI3K/AKT

Introduction The study of the biochemical changes in the brain is particularly difficult because of its unique morphological nature and the relationships between the brain and the other systems of the body. Compared with other organs, the brain appears particularly susceptible to NO, O2, and H2O2 injuries due to its high intake of oxygen (20%) of the whole oxygen in the body to produce ATP, a vital component for neuronal activity, while it is poor in antioxidant defense. Furthermore, neuronal membranes are rich in polyunsaturated fatty acids, which are particularly susceptible to free radical interactions and the elevation of Ca2+ circulation through neuronal membranes and Responsible Editor: Mohamed M. Abdel-Daim * Enas M. Moustafa [email protected] 1

Department of Radiation Biology, National Center for Radiation Research & Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), PO Box 29, Nasr City, Cairo, Egypt

interfering of ion transport rise cytosolic (Ca2+), which activates iNOS in brain and thus the generation of nitric oxide which interact with superoxide to form the toxic peroxynitrite (Cobley et al. 2018). Due to the modern lifestyle triggering an overexposure to reactive oxygen species (ROS), the peopl