Cyclic adenosine-3',5'-phosphate and guanosine-3',5'-phosphate in mouse plasma during administration of chemical compounds with different degrees of radioprotective effectiveness

A study was made of seven radioprotective agents of different chemical classes (sulfur-containing, indolylalkylamines, and imidazol, urea and pyridasine derivatives) and also of their six structural analogs without radioprotective properties on the content of cyclic nucleotides in blood plasma and on the postirradiation survival of mice. There was a correlation between the ability of the preparations to increase the level of cyclic adenosine-3',5'-monophosphate and their radioprotective properties; with guanosine-3',5'-monophosphate, this correlation was absent.     

Effect of isothiuronium alkylamidines and adeturon on the activity of lactate dehydrogenase and its isoenzymes in rat blood serum and organs

A study was made of the effect of four types of S-omega-carboxamidinoalkyl isothiourea, differing in the carbon chain length between amidine and isothiuronium groups, and adeturon on activity of lactate dehydrogenase (LDG) and its isoenzymes in blood serum and organs of rats. Adeturon and compounds with one and three methylene groups elicit a radioprotective effect whereas substances with an even number of methylene groups have no such an effect. The obtained data indicate that changes in activity of LDG and its isoenzymes depend upon the structure of the substance applied. This makes LDG an adequate model in comparative studying the specificity of biochemical effects induced by the radioprotective agents and substances similar in their structure but having no radioprotective efficiency.     

Toxicity and radio-protective properties of pyridazine derivatives

In experiments in irradiated (CBA X S57B1)F1 mice a study was made of toxicity and radioprotective efficiency of some pyridazine and pyridazine dione derivatives. Some of these substances were shown to have a moderate protective action when administered intraperitoneally. A correlation was revealed between the chemical structure and the radioprotective properties of the compounds.     

The antiradiation activity and mechanism of action of dimethylaminodithiazines

A new group of radioprotective agents, dimethylaminodithiazines, was discovered. The agents are effective when used in relatively small amounts and exert a radioprotective effect rapidly with both intraperitoneal and per os injections. The role of inhibition of oxidative processes and DNA biosynthesis in the mechanism of radioprotective action of dimethylaminodithiazines is discussed.     

Mechanism of the radioprotective effect of catecholamine receptor agonists. Inclusion in the radioprotective effect of different subtypes of beta-adrenoreceptors

Isoproterenol of ED50 = 0.16 mumol/kg is highly effective in protecting mice against ionizing radiation and has the high therapeutical index. There are three new indications that isoproterenol exerts its radioprotective action via beta-adrenoceptors. They are: the effect of isoproterenol is prevented by three additional beta-adrenoceptor antagonists, the isoproterenol effect is reproduced by the seven studied beta-adrenoceptor agonists of different chemical structure, and with chemical analogs which fail to stimulate beta-adrenoceptors the radioprotective effect is absent. Both beta 1 and beta 2 adrenoceptor agonists are protective agents. Mechanisms of the radioprotective action are discussed.     

Monoterpene’s multiple free radical scavenging capacity as compared with the radioprotective agent cysteamine and amifostine

Monoterpenes are major active components of lavender, thyme, and mint. The X-ray radioprotective activity of pure monoterpenes is attributed to their scavenging ability against active species, but so far no firm evidence has been demonstrated. The objective of this study is to quantitatively determine antioxidant abilities of monoterpenes and collate it with radioprotective activity. Using multiple free-radical scavenging (MULTIS) method, we have determined the scavenging abilities of monoterpenes (linalool, thymol, and menthol) against six active species. A previous study has shown that the monoterpene linalool is a radioprotector for cellular systems, therefore, its scavenging ability was compared with known radioprotective agents such as cysteamine and amifostine. Results indicated that the monoterpene menthol but not linalool is a potent scavenger of reactive oxygen species and its scavenging magnitude is comparable to cysteamine and amifostine. This paper is first to show a correlation between ROS scavenging ability and radioprotective action.     

Radioprotective properties of oxolinic acid

Oxolinic acid was shown to produce a radioprotective effect on mice and a therapeutic radioprotective action on rats and hamsters. As to radioprotective efficiency, oxolinic acid is inferior to such known sulfur-containing agents as indolylalkylamines and alpha-adrenomimetics. But oxolinic acid has an important advantage over them, that is, the increase in radioresistance it induces persists for several hours. The radioprotective effectiveness of oxolinic acid prompts that it is expedient to search for new radioprotective preparations among specific inhibitors of DNA polymerase of replicative synthesis.     

Chemical protection against genetic effect of radiation in male mice

A study was made of the protective effect of some radioprotective agents against dominant lethal mutations (DLM) in postspermatogonial stages and reciprocal translocations (RT) in spermatogonia induced by gamma-radiation. Among the radioprotective agents used, cystaphos, a combination of cystamine and 5-MOT and a mixture of 6 components proved to be most effective against DLM, and cystaphos, gammaphos and cystamine combined with 5-MOT proved effective against RT. The degree of radioprotective efficacy was relatively low. The efficacy of cystamine in protecting against RT was higher with exposure of gonocytes of 18.5-day embryos than spermatogonia of pubertal animals. The degree of the radioprotective effect varied depending on the stage of spermatogenesis, and, in all cases, it was lower than that observed in studies of protection against lethal effects of ionizing radiation.     

Changes in the therapeutic spectrum with respect to the pharmacological and radioprotective activity after O-alkylation of serotonin and 5(2-hydroxyethoxytryptamine)

In experiments with mongrel mice, a study was made of the pharmacological activity of serotonin and its O-alkyl derivatives. It was estimated by the two indices, that is, the radioprotective properties and the influence on a local blood channel in the spleen, the modifying effect of the agents' toxicity being estimated as well. As an O-alkyl group of 5-alkoxytryptamines was elongated from one to three carbon atoms and the toxicity of the substances increased, their radioprotective effect decreased more readily than their effect on the local blood channel. The shortening of the range of the therapeutic action of the agents under study, with regard to the two pharmacological indices mentioned above, the alkyl group being lengthened, followed a logarithmic function which was more pronounced in relation to the radioprotective index (cos alpha 1/cos alpha 2 = 1.58).     

Effect of electron and steric interactions on the radioprotective properties of indolylalkylamines

Molecular mechanisms of radioprotective action of some substituted indolylalkylamines are discussed in terms of the statistical correlation analysis. It was established that electron and steric properties of the substituents are the factors influencing the radioprotective efficiency of these compounds. It was shown that the correlation obtained, relating the structure of the compounds to the radioprotective effect, may be applied in studies of the mechanism of action of the preparations and for the purposeful synthesis of new compounds.     

Comparative study of the biological properties of various bacterial polysaccharides

It was shown that different polysaccharides markedly vary in their toxicity, exert a radioprotective effect when administered both 24 h and 1-4 h before irradiation, enhance and prolong the radioprotective action of S-containing radioprotective agents, and inhibit DNA synthesis in bone marrow which, in all appearance, plays a certain role in the mechanism of their radioprotective action.     

Characteristics of the role of the hydroxyl group in serotonin in the pharmacological and antiradiation effect of serotonin

It was shown that omega-hydroxylation of O-alkyl serotonin derivatives can slightly improve the radioprotective and pharmacological properties of these substances but fails to remove completely the unfavourable action of O-alkylation of serotonin. There is a close correlation between the radioprotective effect of 5-oxyalkoxytryptamines and their action on blood supply of mouse spleen. The introduction of the alkoxy-group or the tertiary amino-group into omega-position removes the radioprotective effect of 5-alkoxytryptamines.     

Mechanism of mobilization of biogenic amines from rat mast cells in radiation protected conditions

A study was made of the role of calcium ions and some other factors in secretion of biogenic amines from rat mast cells. The data obtained indicate that the radioprotective preparations of indolyl alkylamine and imidazole series can mobilize endogenous radioprotectors. The process of the mediator release from mast cells under the effect of sulfur-containing radioprotective agents is indirect. The molecular mechanisms of mast cell exocytosis are discussed.     

Radioprotective activity of complexes of copper, cobalt and zinc with substituted acylhydrazones

Acylhydrazone metal complexes belong to a new class of radioprotective agents that have a cytostatic effect increasing, in some cases, the survival rate of irradiated animals by 40-60 per cent compared to irradiated controls. The most active drugs are hypotoxic and applied in much lower doses than ordinary S-containing radioprotective agents to achieve the same protective effect.     

The role of endogenous glutathione in the action of sulfur-containing radio-protectors

In experiments on Ehrlich ascite tumor cells, the dependence of the radioprotective effect of beta-mercaptoethylamine and beta-mercaptopropionylglycine on the initial level of endogenous glutathione was studied. A varying degree of N-ethylmaleimide induced decrease of SH-glutathione content in the cells led to either easing or elimination of the radioprotective effect of the agents under study.     

Amino acids and their derivatives as radioprotective agents

Summary Numerous amino acids and their analogs are capable of protecting biological systems from the toxic effects of ionizing radiation. These radioprotective agents can be classified into two broad groups, depending upon the presence or absence of a free or potentially free sulfhydryl group. The sulfhydryl-containing compounds have been studied extensively and are thought to exert their radioprotective effects by several mechanisms, including free radical scavenging and hydrogen atom donation. Several non-sulfhydryl-containing amino acids are also being investigated for their radioprotective effects. These agents are less well known than the familiar sulfhydryl compounds, but possess very interesting protective qualities. In short, the study of amino acids and their derivatives as radioprotective agents continues to contribute to an understanding of processes involved in radiation toxicity and to offer new compounds with potential application to situations of human exposure.     

Radiation protection effectiveness of various zootoxins

A study was made of the effectiveness of a new class of radioprotective agents, polypeptides, obtained from zootoxins of scorpion, tarantula, Lathrodectes tredecimguttatus, and bee under conditions of a short-term and long-term irradiation. The peptide fraction of the scorpion venom, butoxin, was most radioprotective: it provided 65% survival after LD98/30. Butoxin exerted a stimulatory effect on the hypophysis-adrenal system and haemopoiesis of intact and irradiated animals.     

Radioprotective effectiveness and toxicity of 4,5-disubstituted tryptamines

In experiments on mice a study was made of different substituents in the 4th position of the indole ring of 5-methoxytryptamines (5-MOT) on toxicity and radioprotective efficiency of the compounds of this class. It was shown that the administration of the amino-group to a mexamine molecule increased the preparation toxicity; the nitro-group somewhat diminished the toxic properties, and the acetylamino group did not change 5-MOT toxicity. A 5-MOT derivative with a nitro group possessed the strongest radioprotective action. The radioprotective efficiency of these compounds persisted for 1-2 h.     

The modifying action of Sophora japonica and an antioxidant vitamin complex on acute radiation injury to the body]

In experiments with mongrel male rats exposed to whole-body gamma-radiation (7, 9 and 11 Gy) the radioprotective effect of enterally administered Sophora japonica and its combination with an antioxidant vitamin complex was investigated. The radioprotective agents applied were shown to produce a synergistic effect.     

Radioprotective effect of inosine and its enhancement by magnesium and global hypoxia.

The slight radioprotective action of inosine, when injected intraperitoneally to mice shortly before gamma-irradiation, can be enhanced by the administration of magnesium aspartate. This effect can be explained by the additivity of the vasodilatory actions of both agents. Inosine increases the radioprotective effectiveness of hypobaric hypoxia (10% O2), probably due to the additivity of the hypoxic effects in radiosensitive tissues. Acute hypoxic toxicity, however, is decreased by inosine administration. The cumulation of radioprotective effects of inosine and of its antihypoxic action in vitally important organs can have a favourable influence in hypoxic radiotherapy.