Hepatoprotective effect of the radiation countermeasure flagellin in the long term after irradiation of mice.

Purpose: Purpose is to study the hepatoprotective effect of a new promising radiation countermeasure flagellin, in the long term after irradiation. The results of the study can be useful for mitigating the consequences of man-made radiation accidents, protecting professional contingents, reducing the toxic effect of radiation therapy, and expanding the range of drug use.

Materials And Methods: Effect of flagellin was investigated 10 months after its administration of irradiated male of mice F1 (CBAхC57Bl/6).

The Role of Immunomodulator Betaleukin in Recovery of Hepatocytic Ploidy Profile in Delayed Terms after Irradiation.

We studied the radioprotective effect of betaleukin administered to (CBA×C57Bl/6)F1 mice in single doses of 50 and 3 μg/kg 2 and 22 h, respectively, prior to long-term (21 h) whole-body low-intensity (10 mGy/min) γ-radiation (Сs; total dose 12.65 Gy). Hepatocyte ploidy, a biomarker of metabolic disorders of the liver, was evaluated, and nuclearity and ploidy indices were calculated.

Changes in the Activity of Genes Involved in the Regulation of Hematopoiesis during Tumorigenesis in Irradiated Mice.

We used 183 F1 CBA×C57Bl hybrid mice to study the delayed effects of low-power long-term γ-irradiation at a dose of 12.6 Gy (10 mGy/min) 8 and 10 months after the treatment. Eight months after the treatment we found the increased expression of the transcription factor NFκB and its target genes iNOS and G-SCF in the bone marrow (BM).

The Dependence of the Mutagenic Effect on the Dose of X-Ray Irradiation in an In Vivo Experiment on Female (CBA×C57Bl/6)F1 Mice.

We studied the mutagenic effect of X-ray irradiation in doses of 0.5, 1, and 1.5 Gy on female (CBA×C57Bl/6)F1 mice.

[Recombinant thrombopoietin antiradiation therapeutic effectiveness evaluation on dogs according to hemopoiesis and survival criteria].

Recombinant human thrombopoietin (rh TPO) has been investigated as a means of acute radiation disease urgent treatment in the experiments on 24 mongrel dogs. The animals were exposed to total acute gamma-irradiation at the doses of 3.5 Gy (exceeding LD50/45 under our conditions) and 3 Gy.

[Actual problems of searching and studying radiation countermeasures].

The state of radiation counterdrug elaboration has been analyzed. The main criterion of estimation is how various possible radiation incidents are provided with radiation countermeasures. The latter are differentiated in 3 principal groups: radioprotectors, radiomodificators (these are able to have a positive effect when administered preliminary, before the exposure, or provide a delayed nonspecific protection after the exposure--urgent therapy) and hemopoietic growth factors demanding course administration.

[Evaluation of the treatment effectiveness of domestic G-SCF preparations in experiments on irradiated dogs].

We have evaluated the treatment effectiveness of Leucostim and Neupomax in dogs exposed to radiation at lethal doses of 3 and 3.5 Gy, correspondingly, by testing the dynamics of the blood cell number, first of all, leucocytes and neutrophiles, and the 45-day survival. Supportive therapy for all the dogs, including the control ones, consisted in antibiotic treatment during the acute period of 7-24 days.

[Comparison of different G-CSF treatment effectiveness in experiments on irradiated mice].

In the experiments on F1 (CBA x C57BL) and BALB mice irradiated by 137Cs gamma-rays, preparations of unglycosilated G-SCF such as Neupogen and their domestic analogs Leucostim and Neupomax were investigated. The tests such as 9-day bone marrow cellularity (BMC) and endogenous CFUs, the neutrophile number restoration, the 30-day survival index have shown that all three preparations have an approximately equal effectiveness relating to acute radiation disease treatment and granulopoiesis stimulation after a 5-10 day consecutive administration following irradiation of mice at lethal and sublethal doses. We have come to the conclusion that Leucostim and Neupomax can be regarded as adequate substitutes for Neupogen.

[The threshold for radiation stochastic effects: arguments "pro" and "contra". Applied realization].

This study represents the analysis of the data available in the literature and the author's findings concerning the issue of a shape of the dose stochastic effect curve in the range of low levels of radiation (LLR). The data obtained from radioepidemiological and experimental investigations are used. Also considered are the arguments "pro" and "contra" regarding approximation of these curves by means of a linear function (linear non-threshold conception) or as a quasi-plateau (threshold conception).

[Radiobiological analysis of cancerogenic risk values in radioepidemiological investigations].

The aim of the present article consisted in critical analysis of the epidemiological approach to radiocancerogenic risk estimation in region of low level radiation (LLR). The estimation is making by means of mathematician models that ignore a principal difference in biological action of LLR and high level radiation (HLR). The main formal characteristic of LLR action is the presence of a plateau in beginning of a dose-effect curve of radiogenic risk.

[The analytical review of the schemes of the acute radiation disease treatment used in experiment and in clinic].

The analysis of the original sources showed that there are some differences in approaches to radiation injuries treatment used mainly by Russian and foreign researches in their experiments. In Russian radiobiology the main way was the single usage of high molecular substances of different chemical structure and of natural origin soon after radiation exposure. These substances were designated then as cytokine inductors.

[Recombinant human interleukine-1beta (betaleukine) usage for acute radiation sickness of severe degree treatment at canines].

Recombinant human interleukine-1beta (betaleukune) of Institute of especially pure biopreparation production had been examined as a treatment means at acute radiation disease of severe degree at dogs. Dogs were irradiated totally in doses above the LD95/45. Betaleukine had been administered s/c twice in day in 15 min - 2 h after irradiation.

[Analysis of the epidemiological data concerning radiation carcinogenic effects and approaches to the low doses' upper limits determination in the aspect of a threshold of the unhealthy influences of ionizing radiation].

The analysis of the epidemiological data regarding cancer mortality in cohorts of Japanese A-bomb survivors and Chermobyl liquidators exposed to different doses suggests that there are good reasons for recognizing the threshold of the radiocarcinogenic effect in the region of about 200 Gy (mSv). The analysis of solid cancer mortality in Japanese cohort, which exceeded the expected one in a dose diapason of 5-200 mSv, revealed a (quasi) plateau in a dose-effect curve and led to the conclusion that the nature of the overshoot is non-radiogenic. The analysis of supposedly dose dependent leucosis incidence in the limited low dose diapason in the Chernobyl cohort showed that the real coefficient of the excess absolute or relative radiation risk could not be received in the case because the larger part curve was placed under the control level.

[Dependence of the therapeutic effectiveness of interleukin-1beta on the time of the drug administration after irradiation of mice].

In experiments on mice F1(CBA x C57BL/6) the dependence of 30th days survival on the time of betaleukin (medicine form of interleukin-1 beta) administering after exposure to 7.5 Gy whole body gamma-irradiation from 137Cs (approximately DL80/30) was studied. Betaleukin was injected subcutaneously in dose 25 mcg/kg 0.

[Study of mechanisms of anti-irradiation effects of interleukin-1beta in long-term bone marrow cultures].

The influence of betaleukin (human recombinant interleukin-1 beta) on the processes of postirradiation recovery of haemopoietic precursors (GM-CFC) and the level of granulocyte-macrophag colony-stimulating factor (GM-CSF) were studied in long-term bone marrow cultures after gamma-irradiation with a dose 2 Gy. Then the betaleukin action on the contents of GM-CFC and induction of GM-CSF in the non irradiated cultures was studied. It was shown that betaleukin increased the induction of GM-CSF and raised the contents of GM-CFC in long-term bone marrow cultures, and the maximal increase of a GM-CSF level and GM-CFC amount was marked in 20 hours after introduction.

[Pro and contra regarding the threshold/non-threshold mutagenic (carcinogenic) action of low-level ionizing radiation].

According to the analysis of epidemiological and experimental data there are evidences in threshold on criterion of mutagenic (in broad sense) ionising radiation action. A threshold takes place in the region of about 20-200 mGy concerning a dose in case of an acute exposure and in the region of the third order above a background level regarding a dose rate in case of chronic or prolonged exposure. Evidences in favour of linear non-threshold conception are based on primitive mathematical extrapolations and approximations of the study results, mainly, in the region of intermediate doses/dose rates.

[Biological effects of low level ionizing radiation (the threshold of effects and radiosensitivity/radioreactivity of biological structures with different level of organization)].

There have been analysed the data as own as taken from the literature concerning the action of low level radiation (LLR) on different structure level in a mammalian organism. There have been compared the types of various structures early reactions regarding an acute or prolonged exposure depending on the test type and the studied structure organization level. The data analysis has shown it should differentiate the damaging and irritating action of LLR.

[The estimation of the level of mutations at the glycophorin A locus in subjects exposed to the chronic action of ionizing radiation].

11 persons, who had been irradiated chronically at low dose rate under occupational conditions in 1950s in doses 220-581 cGy according data of individual film dosimeters, and 5 control persons were examined regarding the level of glycophorin A (GPA) mutation type NO and NN in blood erythrocytes. Significantly higher level of GPA mutations type NO was registered in average in the group of exposed persons (23.2 +/- 4.

[Cytokines in the aspect of pathogenesis and therapy of acute radiation sickness].

The statement about dominating role of stem cell failure (exhaustion) in acute radiation bone marrow syndrome outcome needs to be changed. Cytokine-producing cells lacking reactivity that prevent usage of stem cell compartment reserves can play important role in immunohemopoiesis radiation damage.

[Radiobiological, clinical, experimental and methodological aspects of postradiation repair of hematopoietic stem cells].

On the basis of literature and author's data the topics dealt with revealing and evaluation of post-radiation repair as well as possibility of its acceleration in hemopoietic stem (colony-forming) cells are presented and discussed. Some conceptions formed in this field of science cannot be regarded as final ones and should be checked by means of different independent methods. Evaluation of stem cell repair pronouncing and its acceleration possibility is rather indefinite.

[Rapid metabolic changes in the blood and organs of rats under the influence of electron pulse radiation at superhigh doses].

Early metabolic changes have been studied in the peripheral blood, brain, adrenals, spleen, and liver of rats after irradiation with 500 Gy. Using ESR spectroscopy we showed the formation of a great amount of hemoglobin nitrosyl complexes and methemoglobin in the blood and spleen, thus suggesting that the endothelium-derived relaxing factor, nitric oxide (NO), was released due to irradiation stimulation and sharp hypoxia in brain. Polarographic data concerning the disturbance of brain mitochondrial function (activation of succinate hydrogenase oxidation) allowed a conclusion that hypoxia appeared after irradiation at superlethal doses.

[The essential questions of constructing a theory of radioprotective action on the body].

The most disputable points of an universal hypothesis concerning radioprotective action are discussed. The attention is focused on the question whether it is necessary to differ the ways of radioresistance development in organism and the sites of its realization to the radioprotective effect.

[The significance of the cellular factor in realizing the restorative effect of the procedure of bone marrow exfusion, incubation and reimplantation in irradiated mice].

In experiments with F1 (CBA X C57Bl) mice irradiated with doses of 6.5 to 8.5 Gy the evidence was obtained for the important role of the reimplanted cells in a complete realization of the reparative effect of exfusion, incubation and reimplantation of bone marrow.

[The effect of mexamine on liver mitochondrial function in rats in vivo and in vitro from the aspect of the mechanisms of the pharmacological and radioprotective action of the protector].

The polarographic study of the functional status (FS) of rat liver mitochondria subjected to the effect of mexamine in vivo and in vitro and the hypoxic hypoxia in vivo has revealed various FS changes displaying disconnecting and rotenone-like effects and posthypoxic activation. With a mexamine dose of 50 mg/kg in vivo the direct effect of the protector contributes considerably to the mitochondrial FS. Within a wide range of mexamine doses no relationship was found between the pattern of the mitochondrial FS change in the liver and the protective effect with respect to bone marrow.