Role of Bioenergy Effects of Cystamine in Implementing Potentiation of Radioprotective Properties of the Radioprotector under Repeated Administration

An early phenomenon on the potentiation of the radioprotective properties of aminothiols (cystamine) during repeated application in the first 7 h of the after-effect of a drug by increasing the activity by two times was discovered (B.I. Davydov, 1971; M.V. Vasin and V.V. Antipov, 1972). A hypothesis has been proposed to explain this phenomenon. The mechanism of radioprotective properties of cystamine is associated with partial neutralization of oxygen effect with the development of reductive stress in the cell, which does not end after the cessation of the protective effect of the radioprotector. In the body, negative feedback mechanisms are implemented in the cell, which prevent full implementation of naked consequences of reductive stress. In it, the transcription factor HIF-1 plays a key role, which enhances the production of ATP due to glycolysis and, thereby, reduces the burden on oxidative phosphorylation processes under conditions of acute hypoxia. With repeated use of cystamine in the first seven hours of its aftereffect after the cessation of its antiradiation activity, there is an increase in the manifestation of restorative stress in the form of metabolic shifts with the development of deep hypothermia in animals up to 29°C rectal temperature, which prevents the implementation of the action of HIF-1. These processes contribute to a more complete implementation of post-radiation reparation of DNA breaks by providing more time for it under conditions of longer hypothermia and mitotic blockade under the action of cystamine.