The impact of citicoline on brain mitochondrial dysfunction induced in rats after head irradiation.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Cytidine Diphosphate Choline*/pharmacology ; Mitochondria*/drug effects ; Mitochondria*/metabolism ; Mitochondria*/radiation effects ; Mitochondria*/pathology ; Brain*/drug effects ; Brain*/radiation effects ; Brain*/metabolism ; Brain*/pathology; Animals ; Rats ; Male ; Oxidative Stress/drug effects ; Oxidative Stress/radiation effects ; Gamma Rays/adverse effects ; Calcium/metabolism ; Acetylcholinesterase/metabolism ; Iron/metabolism ; Rats, Wistar ; alpha7 Nicotinic Acetylcholine Receptor/metabolism ; alpha7 Nicotinic Acetylcholine Receptor/genetics ; Apoptosis/drug effects ; Apoptosis/radiation effects ; Caspase 3/metabolism ; Adenosine Triphosphate/metabolism

Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: All animal procedures were carried out according to the international guidelines of animal handling and care published by the National Institute of Health (NIH no. 85:23, 1996) and in compliance with the ARRIVE guidelines. The study protocol was approved by the Animal Ethics Committee of the National Center for Radiation Research & Technology (56 A/23).
Head irradiation is a common treatment for brain cancer; however, it can cause side effects in healthy brain tissue. This study aimed to test whether citicoline administration modulates radiation-induced brain mitochondrial dysfunction in rats. The head of the animal was exposed to 10 Gy γ-radiation. Citicoline (300 mg/kg body weight/day) was administered intraperitoneally for four weeks after irradiation. Some biochemical changes related to mitochondrial function in brain tissue were studied. The results showed that citicoline administration after head irradiation reduced oxidative stress, enhanced the activity of mitochondrial complexes (I and II), increased the aconitase enzyme activity, boosted ATP production, and restored the levels of calcium, iron, and caspase-3, compared to the corresponding values in irradiated rats. The levels of glucose and cholesterol in brain tissue were modulated. Citicoline also increased acetylcholine level and alpha-7 nicotinic receptor mRNA expression and decreased acetylcholinesterase activity in the brain tissue of irradiated-treated rats. We concluded that citicoline could attenuate the harmful effects of γ-radiation on the brain by modulating mitochondrial function, neurotransmission, and calcium & iron homeostasis, thus suppressing the mitochondrial-mediated apoptosis pathway. However, additional studies are required to validate and confirm these results before any clinical application can be recommended.
(© 2025. The Author(s).)

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Keywords: Citicoline; Mitochondria; Oxidative stress; γ-Radiation

536BQ2JVC7 (Cytidine Diphosphate Choline)
SY7Q814VUP (Calcium)
EC 3.1.1.7 (Acetylcholinesterase)
E1UOL152H7 (Iron)
0 (alpha7 Nicotinic Acetylcholine Receptor)
EC 3.4.22.- (Caspase 3)
8L70Q75FXE (Adenosine Triphosphate)

Date Created: 20250715 Date Completed: 20250716 Latest Revision: 20250718

20250718

PMC12263842

10.1038/s41598-025-11098-4

40665089