The Effect of Ionizing Radiation on the Creatine–Creatine Kinase System in the Rat Brain and the Radioprotective Effect of Creatine

Abstract

Abstract—Creatine kinase (CK) and its substrates creatine (Cr) and creatine phosphate (CrP) form the Cr–CrP–CK system, which, along with its buffer and transport roles in the energy metabolism of the cell, also performs the function of maintenance of the stability of mitochondrial membranes, which together determines the neuroprotective role of Cr. Considering the anti-apoptotic and antioxidant properties of Cr, as well as the fact that oxidative stress is the basis of radiation damage, we studied (1) the effect of ionizing radiation on the dynamics of post-radiation changes in CK activity and Cr content in outbred rats after their irradiation with a sublethal dose of 4.5 Gy in the presence and absence of Cr and (2) the radioprotective efficacy of Cr for the Cr–CK system of the brain and the survival rate of rats after irradiation at a LD_70/30 dose equal to 6.3 Gy. The data we obtained showed a high degree of radiosensitivity and adaptability of the Cr–CK system of the brain, as well as a significant radioprotective efficacy of Cr, both in relation to the Cr–CK system of the brain and the survival rate of rats. The radioprotective effect of Cr calculated using the Kaplan–Meier statistical survival model was 38.6% for the group that received the Cr in 0.9% glucose solution compared to the control group that received water instead of Cr and 30.3% compared to the control group treated with 0.9% glucose. For the group that received the aqueous solution of Cr, the effect was smaller, 20.5% compared with the corresponding control group, which is obviously related to the relatively worse availability of the Cr to cells from the aqueous solution.