Role of Bioenergy Effects of Cystamine in Realising Potentiation of Radioprotective Properties of the Radioprotector in its Repeated Administration

Abstract

Early phenomenon on the potentiation of radioprotective properties of aminothiols (cystamine) during repeated application in the first 7 h of drug’s after-effect by increasing their activity by 2 times was discovered (B.I. Davydov, 1971, M.V. Vasin, V.V. Antipov, 1972). A hypothesis has been proposed to explain this phenomenon. The mechanism of radioprotective properties 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 protective effect of radioprotector. In the body, negative feedback mechanisms are implemented at 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 over the first 7 h after the cessation of its radioprotective activity. There is an increase in metabolic shifts in the body with the development of deep hypothermia in animals up to 29°C rectal temperature which can lead to depletion of these restrictive mechanisms and, thereby allowing aminothiol to fully exhibit its protective properties without excluding the increase in its toxicity. In addition, this contributes to a more complete implementation of post-radiation repair of DNA. These processes contribute to a more complete realization of the affected repair of DNA breaks by providing more time for it in conditions of longer hypothermia and mitotic blockade under the action of cystamine.