Radioprotective effect of cyclo(L-phenylalanyl-L-prolyl) on irradiated rat lung

In the present study, we investigated the radioprotective effect of cyclo(L-phenylalanyl-L-prolyl) on irradiated rat lungs to determine its potential as a radioprotective agent. We found that early lung damage induced by irradiation was reduced by treatment with 40 mg/kg of cyclo(Lphenylalanyl- L-prolyl) in the latent and early pneumonitis phases. Expression of TNF-alpha and TGF-beta1 at 2 and TGF-beta1 at 8 weeks post-irradiation was decreased in animals that received both radiation and cyclo(L-phenylalanyl-L-prolyl) compared with animals that received radiation alone. Evidence indicated that the proinflammatory cytokine TNF-alpha and the fibrogenic cytokine TGF-beta1 likely play a role in the radioprotective effect of cyclo(L-phenylalanyl-L-prolyl). However, besides TNF-alpha and TGF-beta1 expressions, the precise mechanism by which cyclo(L-phenylalanyl-L-prolyl) ameliorates the induced radiation damage is not clear.     

Oxygen effect and cellular glutathione

A study was made of the influence of binding of endogenous nonprotein thiols (glutathione, GSH) by N-ethylmaleimide before or after irradiation (7 Gy) of Ehrlich ascites tumor cells on the radioprotective effect of anoxia (argon, 0.003% O2). It was shown that the radioprotective effect of anoxia decreased as cell glutathione was removed before or after irradiation (similarly both immediately and 1 h after irradiation). Inspite of the fact that the GSH level decreased similarly before and after irradiation the radioprotective effect of anoxia was less pronounced in the latter case. The data obtained permit to evaluate quantitatively the contribution of endogenous GSH to the processes occurring at the time of irradiation and during the post-irradiation period.     

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.     

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.     

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.     

Antioxidant vitamins C, E and beta-carotene reduce DNA damage before as well as after gamma-ray irradiation of human lymphocytes in vitro

The protective effect of Vitamins C, E and beta-carotene against gamma-ray-induced DNA damage in human lymphocytes in vitro was investigated. Cultured lymphocytes were exposed to increasing concentration of these vitamins either before or after irradiation with 2Gy of gamma-rays and DNA damage was estimated using micronucleus assay. A radioprotective effect was observed when antioxidant vitamins were added to cultured cells before as well after irradiation; the strongest effect was observed when they were added no later than 1h after irradiation. The radioprotective effect of vitamins also depended on their concentration; Vitamins C added at low concentration (1 microg/ml) before exposure of the cells to radiation prevented induction of micronuclei. Vitamin E at the concentration above 2 microg/ml decreased the level of radiation-induced micronuclei when compared to the cells irradiated without vitamin treatment. beta-Carotene was effective at all tested concentrations from 1 to 5 microg/ml and reduced the number of micronuclei in irradiated cells. The vitamins had no effect on radiation-induced cytotoxicity as measured by nuclear division index. The radioprotective action of antioxidant Vitamins C, E and beta-carotene was dependent upon their concentration as well as time and sequence of application.     

Quercetin ameliorates gamma radiation-induced DNA damage and biochemical changes in human peripheral blood lymphocytes

We investigated the radioprotective efficacy of quercetin (QN), a naturally occurring flavonoid against gamma radiation-induced damage in human peripheral blood lymphocytes and plasmid DNA. In plasmid study, QN at different concentrations (3, 6, 12, 24 and 48 microM) were pre-incubated with plasmid DNA for 1h followed by exposure of 6 Gy radiation. Among all concentrations of QN used, 24 microM showed optimum radioprotective potential. To establish the most effective protective concentration of QN in lymphocytes, the cells were pre-incubated with 3, 6, 12, 24 and 48 microM of QN for 30 min and then exposed to 4 Gy gamma-radiation. The concentration-dependent effects of QN were evaluated by scoring micronuclei (MN) frequencies. The results showed that QN decreased the MN frequencies dose dependently, but the effect was more pronounced at 24 microM. Thus, 24 microM of QN was selected as the optimum concentration and was further used to evaluate its radioprotective effect in lymphocytes. For that a separate experiment was carried out, in which lymphocytes were incubated with QN (24 microM) for 30 min and exposed to different doses of radiation (1, 2, 3 and 4 Gy). Genetic damage (MN, dicentric aberration and comet attributes) and biochemical changes were measured to evaluate the effect of QN on gamma-radiations (1-4 Gy). Radiation exposed showed significant increases in the genetic damage and thiobarbituric acid reactive substances (TBARS) accompanied by a significant decrease in the antioxidant status. QN pretreatment significantly decreased the genetic damage and TBARS and improved antioxidant status through its antioxidant potential. Altogether, our findings encourage further mechanistic and in vivo studies to investigate radioprotective efficacy of QN.     

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).     

Mechanism of the radioprotective effect of catecholamine receptor agonists. Inclusion in the radioprotective effect of both subtypes of alpha-adrenoreceptors

alpha-Adrenoceptor agonists of both main groups, i. e. arylalkylamines and imidazolines, have a pronounced radioprotective effect. Their chemical analogs, which fail to stimulate alpha-adrenoceptors, do not protect mice. The effect of phenylephrine, adrenaline, and noradrenaline comes into play via alpha 1-adrenoceptors and that of clonidine, via alpha 2-adrenoceptors and also via alpha 1-adrenoceptors. Adrenoceptor agonists can probably manifest their radioprotective action via both subtypes of alpha-adrenoceptors. Possible intracellular mechanisms of the radioprotective action are discussed.     

Comparative characteristics of the modification of radiosensitivity of mice and rats by a hypoxic mixture

A comparative study was made of changes in radiosensitivity of mice and rats given hypoxic mixtures (GHM) containing 6 to 15% of oxygen. The radioprotective effect of the GHM was more pronounced in mice than rats. The dependence of the radioprotective effect of the GHM on the oxygen content was well approximated by the equations: (Formula: see text). In experiments on rats, the oxygen content of 13.8% was shown to be a threshold the exceeding of which removed the modifying effect of the GHM.     

Synthesis of some thiourea derivatives and their influence on biological and genetic effects of gamma rays

The synthesis of the new radioprotective compounds ATB (I, 2-allylthioureidobenzoic acid), PTB (II, 2-phenylthioureidobenzoic acid), A-2-PTU (III, N-allyl-N'-2-pyridylthiourea), and P-2-PTU (IV, N-phenyl-N'-2-pyridylthiourea) and their influence on biological and genetic effects of gamma rays was studied. In result of investigations it must be noted that PTB displayed radioprotective effect as a result of which more plants in M1 germination and survive in M2 of the induced mutations is increased. The cytological analysis reveals that the studied substance (PTB) decreases chromosome aberration in meristem cells of pea roots almost twice as a result of postirradiation treatment. The effect of A-2-PTU in the experiments with peas greatly depends on the dose of irradiation, i.e., on the degree of damaging of the processes of cell restoration and the possibility of their partial restoration after the treatment with the protector. The results obtained suggest that chemical compounds of N,N'-disubstituted thiourea group (A-2-PTU and P-2-PTU) exert strong radioprotective effect in the experiments with peas. This is of great importance to modern radiobiology and radiation mutagenesis and also to protect hereditary structures against radiation.     

Manifestation of oxygen effect during normobaric hypoxic hypoxia in the intrauterine and postnatal developmental periods]

The experiments on rats have shown that hypoxic gas mixture containing 10% of oxygen and 90% of nitrogen (HGM-10) under normobaric conditions exerts a highly reliable radioprotective effect on progeny when 11-day pregnant animals are exposed to total irradiation (60Co, 20 Gy). As distinct from the known radioprotector, mexamine, (5-methoxytryptamine), HGM-10 has a pronounced radioprotective effect during the first days (1-5) after birth. Radioresistance of new-born rats correlates with the level of pO2 in the tissues which progressively decreases with respiration of HGM-10 and remains unchanged after mexamine (10 mg/kg) introduction.     

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.     

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.     

The effect of recombinant human interleukin-1 beta on the repopulation of bone-marrow colony-forming cells in mice subjected to the action of radiation and burns]

The radioprotective and restorative (therapeutic) effects of human recombinant interleukin-1 beta (IL-1 beta) on the population of bone marrow CFU-S of mice, subjected to either sublethal doses of ionising irradiation itself or the same irradiation in combination with thermal burn, are investigated. Both the effects of the agent are registered under both in vitro and in vivo irradiation in semi-, syn- and allogeneic animals. If the irradiation was combined with thermal burn, the "therapeutic" effect of the agent was demonstrated at irradiation dose equal to 3.06 Gy rather than to 6.12 Gy. If the bone marrow cells were irradiated in vitro in dose 3.06 Gy with the following heat shock at 42 degrees C for 10-20 min, the "therapeutic" effect of IL-1 beta was seen only if it was added to cells before rather than after irradiation. The radioprotective effect of IL-1 beta is maintained under in vitro, as well as in vivo conditions in the allogeneic system of transplantation of the CBA donor bone marrow to the C57BL mice.     

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.     

Radioprotective effect of nucleosides and nucleotides and the mechanism of action of adenosine

Adenosine and a majority of adenine mononucleotides have a radioprotective action; adenine and 2'-deoxyadenosine have no radioprotective effect, and that of 3',5'-cAMP only approaches the detectable level. Ribo- and deoxyribonucleosides and nucleotides of guanine, uracil, thymine, and cytosine have no protective action. Dipyridamole increases and alkylxanthines block the radioprotective effect of adenosine. So it follows that the radioprotective effect is realized via A-receptors of the plasmatic membrane external surface.     

Radioprotective action of catecholamines on a Chinese hamster fibroblast culture

The radioprotective ability of adrenaline, noradrenaline and isoproterenol in various concentrations has been studied in experiments on cultured Chinese hamster fibroblasts in vitro. Radioprotective effect of isoproterenol is pronounced at 10(-8)M concentration; adrenaline and especially noradrenaline are effective at higher concentrations. The antagonist of beta-adrenergic receptors propranolol blocks the radioprotective effect of catecholamines on cells. The beta-adrenergic mechanism of catecholamines radioprotective action on the mammals cells is under discussion.