A method for radioprotective effect evaluation

The method here proposed is based on the prevention of photodynamic yeast cell damage by substances possessing radioprotective activity.The photodynamic yeast inactivation was achieved with Toluidine Blue as the photosensitizer and white exciting light. The model radioprotectors tested, namely, WR2721 [S-2(3-aminopropylamino)ethylphosphorothioic acid] and AET [2-aminoethylisothiouronium bromide], were applied at concentrations ranging from 0 to 200 mg/L. Under the conditions of photodynamic damage WR2721 and AET demonstrated a protective effect as evaluated by the enhancement of the cell survival and colony formation. The protection achieved by AET was more effective. The dependence of the protective effect on the concentration of both agents was linear in the low concentrations range.Experiments with radioprotective preparations of yeast origin demonstrated a similar relationship between the concentration and cell survival.These results indicate that the prevention of the photodynamic yeast cell damage by radioprotectors can find an application as a method for determination of radioprotective effects demonstrated by biotechnologically obtained substances in the course of their production and purification.     

Mechanism of the radioprotective effect of cysteamine

The radioprotective effect of cysteamine combined with the modification of the chromatin state by sodium butyrate has been studied using V-79 and CHEL lines of Chinese hamster cells and HeLa cells. Sodium butyrate enhances the chromatin sensitivity to nucleases and removes the radioprotective effect of cysteamine as measured by the yield of cells with chromosome aberrations. As is indicated by changes in the intensity of fluorescence of the DNA-ethidium bromide complex, measured by laser flow cytometry, the protective agent decreases the binding of the dye with both irradiated and nonirradiated DNA whereas ionizing radiation and sodium butyrate increase thereof. It is concluded that the radioprotective effect of cysteamine depends in its ability to reduce the susceptibility of DNA to nucleases.     

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.     

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.     

In vivo radioprotective effect of Moringa oleifera leaves

Radioprotective property of Moringa oleifera leaves was investigated in healthy adult Swiss albino mice. Animals were injected (ip) with 150 mg/kg body weight of 50% methanolic extract (ME) of M. oleifera leaves, as a single dose, or in 5 daily fractions of 30 mg/kg each, and exposed to whole body gamma irradiation (RT, 4 Gy) 1 hr later. Five animals from each group were sacrificed at 1, 2 and 7 days after treatment. Bone marrow protection was studied by scoring aberrations in metaphase chromosomes and micronucleus induction in polychromatic erythrocytes and normochromatic erythrocytes. Pretreatment with a single dose of 150 mg/kg ME significantly reduced the percent aberrant cells to 2/3rd that of RT alone group on day 1 and brought the values to normal range by day 7 post-irradiation. A similar effect was also seen for the micronucleated cells. Fractionated administration of ME (30 mg/kg x 5) gave a higher protection than that given by the same dose administered as a single treatment. ME also inhibited the Fenton reaction-generated free radical activity in vitro in a concentration dependent manner. These results demonstrate that pretreatment with the methanolic leaf extract of M. oleifera confers significant radiation protection to the bone marrow chromosomes in mice and this may lead to the higher 30 day survival after lethal whole body irradiation.     

The radioprotective effect of riboxine (inosine)

In experiments with mice subjected to whole-body X-irradiation a radioprotective effect of riboxine (inosine) was demonstrated. The observed effect may be attributed to the ability of the preparation to interfere with the cyclic nucleotide metabolism.     

Mechanisms of the radioprotective effect of cysteamine in Escherichia coli

The values of the oxygen effect (m) and the maximal protective effect of cysteamine (DMF*) were estimated for four Escherichia coli strains: AB1157 (wild type), AB1886 (uvrA), AB2463 (recA), and p3478 (polA). A correlation made between DMF* and m as well as the kinetics of the increase of DMF with oxygen depletion showed that the protective effect of cysteamine is realized by three mechanisms: (i) anoxia achieved by oxygen reduction, with the DMF varying from 2.2 to 4.2 for different E. coli strains (this protection is the major contribution to the entire mechanism); (ii) lowering of the indirect radiation effect; i.e., for 50 mM cysteamine DMF does not exceed 1.1; and (iii) increase of the efficiency of enzymatic repair. The latter effect of cysteamine is registered only with the wild-type E. coli, the DMF being not less than 1.4.