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

Abstract

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.

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

Fig. 1

Free radicals in rat brain tissue and Malondialdehyde and glutathione levels in rat brain mitochondria following head irradiation and/or citicoline administration. Data are expressed as means ± standard deviation (n=6). ^a: Significance versus Control. ^b: Significance versus Radiation. The mean difference is significant at the 0.05 level.

Fig. 2

Glucose, Cholesterol, Triglycerides, low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), and Total protein levels in rat brain tissue following head irradiation and/or citicoline administration. ^a: Significance versus Control. ^b: Significance versus Radiation. The mean difference is significant at the 0.05 level.

Fig. 3

Acetylcholine level, alpha7nicotinic acetylcholine receptor (α7nAChR) mRNA expression, and Acetylcholinesterase activity in rat brain tissue following head irradiation and/or citicoline administration. Data are expressed as means ± standard deviation (n = 6). ^a: Significance versus control. ^b: Significance versus Radiation. The mean difference is significant at the 0.05 level.