Abstract

The potential mechanisms of radioprotective effect of radiomodulators as agents of “biological” protection against oxidative stress in conditions of acute and chronic irradiation at high- and low-dose-rate ionizing radiation are considered. Radiomodulators, as natural antioxidants, prevent lipid peroxidation of cell membranes and reduce radiation toxemia. The radioprotective and radiomitigative properties of natural antioxidants are limited in terms of a dose reduction factor of 1.15–1.2. The dose–effect interrelation of antioxidants has a dome-shaped character; they can be prooxidants under certain conditions. With this mechanism they are also able to reduce acute toxicity of medicines and poisons. Long, low-intensive radiation at more than 100 mSv/year causes the development of oxidative stress with activation of the mechanisms of antioxidant defense upon its further exhaustion with a decrease in the ascorbic acid content in tissues and endogenous reduced thiols. In this case, the use of natural antioxidants allows a reduction in manifestations of oxidative stress via substrate therapy, thereby compensating for vitamin deficiency under the conditions of their intense consumption. At the same time, the delivery of exogenous purine nucleoside favors the synthesis of DNA and RNA in the course of their postradiation repair. In the condition of oxidative stress, the basis of adaptation shifts in the antioxidant system eventually consists of activation of the nuclear factor Nrf2 and NAD-dependent histone deacetylases sirtuins. Via hormesis, plant polyphenols, coumarins, purine nucleosides, and melatonin can modulate the Nrf2 nuclear factor and sirtuin activity and reduce the remote consequences of chronic radiation exposure, such as a reduction of the human lifespan, by a delay of the development of atherosclerosis, cardiovascular, and neurodegenerative diseases, metabolic syndrome, diabetes mellitus, and the risk of carcinogenesis.

中文翻译：

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放射性调节剂作为电离辐射影响下抗氧化应激的生物保护剂

摘要

考虑了在高剂量率和低剂量率电离辐射的急性和慢性照射条件下，放射性调节剂作为抗氧化应激的“生物”保护剂的潜在辐射防护机制。放射性调节剂作为天然抗氧化剂，可防止脂质过氧化细胞膜并减少辐射毒血症。天然抗氧化剂的辐射防护和放射缓解特性受剂量减少系数1.15–1.2的限制。抗氧化剂的剂量效应相互关系具有圆顶状特征。它们在某些条件下可以是抗氧化剂。通过这种机制，它们还能够减少药物和毒药的急性毒性。长，每年超过100 mSv的低强度辐射会导致氧化应激的发展，并在其进一步耗尽时激活抗氧化剂防御机制，从而降低组织中抗坏血酸的含量并减少内源性还原硫醇。在这种情况下，使用天然抗氧化剂可通过底物疗法减少氧化应激的表现，从而在其大量食用的条件下弥补维生素的缺乏。同时，外源嘌呤核苷的递送有利于在放射后修复过程中DNA和RNA的合成。在氧化应激的条件下，抗氧化剂系统中适应性转变的基础最终包括核因子Nrf2和NAD依赖性组蛋白脱乙酰酶sirtuins的激活。通过兴奋剂，