Model of Accelerated Aging in CB6F2 Mice Induced by Ionizing Radiation.

A model for accelerated aging in mice was developed: CB6F2 mice aged 39-45 days were exposed to fractionated 4-fold relatively uniform γ-radiation (137Cs, 0.98 Gy/min) at a total dose of 6.8 Gy. Radiation exposure led to delayed active growth, leukopenia, and lymphopenia for over 1 year during the post-radiation period. The death of irradiated males and females occurred significantly earlier than in control group animals. Median lifespans in the experimental group were 35-38% lower than in the control group (p<0.001). Ionizing radiation exposure led to the early development of hair depigmentation, cachexia, and the development of aging-associated diseases. In irradiated mice, oncological pathology constituted 30-35% in the mortality structure, which is twice as often as in the control group. The developed model can be used to study the pathogenesis of accelerated aging under radiation exposure and the search for means of its prevention and treatment.

Evaluation of the genotoxic and antigenotoxic potential of lignin-derivative BP-C2 in the comet assay in vivo.

The genotoxic and antigenotoxic potential of BP-C2, a novel lignin-derived polyphenolic composition with ammonium molybdate, was investigated as a radioprotector/radiomitigator for civil applications and as a medical countermeasure for radiation emergencies. Using the alkaline comet assay and methyl methanesulfonate (MMS, 40 mg/kg) as the DNA-damaging agent, these effects of BP-C2 on liver, bone marrow cells and blood leukocytes in rats were studied. The DNA damage was estimated by the DNA content in the comet tail (TDNA, %) 1, 6 and 18 h post exposure to MMS. BP-C2 at doses of 20, 200 and 2000 mg/kg did not exert genotoxic activity in the tested tissues in rats. BP-C2 administered at doses of 20, 100 and 200 mg/kg 1 h before MMS significantly (p < 0.01) mitigated MMS-induced DNA damage, showing a strong genoprotective effect in the liver. In blood leukocytes and bone marrow samples of animals treated with BP-C2, the TDNA % was slightly higher than in the negative control (vehicle) but significantly lower than in the positive control (MMS). Thus, BP-C2 exerted a genoprotective effect against MMS-induced DNA damage to a greater extent towards liver cells, requiring further evaluation of this substance as a genoprotective agent.

[Radiation-protective agent and anti-aging agents: random and predictable matches.]

Radiation-protective and anti-aging properties are often combined. Combination of this properties is linked to the common mechanisms of action such as direct and indirect antioxidant activities, inhibition of free radicals formation, increase resistance to stress impacts at the cellular level, acceleration of DNA reparation, prevention of chronic diseases linked to abnormalities in regeneration processes, activation of immune inflammatory processes and carcinogenesis. Regulation of cell cycle and apoptosis can often be considered as an implementing driver of radiation-protective and anti-aging activities. On the one hand, against the background of stopping the cell cycle and blockade of apoptosis increases the time required to repair the defects of a DNA. Antiapoptotic effects enhances survival chances at the early stage after irradiation in a particular range of doses. On the other hand, activation of apoptosis of altered cells can be seen as one of the mechanisms to delay aging processes and prevention of isolated effects of exposure to ionizing radiation. Formation of radiation-induced and age-related alterations are characterized by multiple factors and a variety of manifestations. Nevertheless, similarity of individual links of the pathogenesis of disease related to radiation exposure and aging of the body is striking. It could be stated that radiation-protective property defines an increase in life expectancy by short-term exposure in sub-lethal and lethal doses. However anti-aging activities prevent the development of remote effects of ionizing radiation by prolonged low doses or fractionated exposure to radiation.

Exploring bioactivity potential of polyphenolic water-soluble lignin derivative.

Many natural substances exhibit anti-inflammatory activity and considerable potential in prophylaxis and treatment of allergies. Knowing exact molecular targets, which is required for developing these as medicinal products, is often challenging for multicomponent compositions. In the present study we examined novel polyphenolic substance, a water-soluble fraction of wood lignin (laboratory code BP-Cx-1). In our previous study, a number of polyphenolic components of BP-Cx-1 (flavonoids, sapogenins, phenanthrenes etc.) were identified as the major carriers of biological activity of BP-Cx drug family, and several molecular targets involved in cancer and/or inflammation signaling pathways were proposed based on the results of the in vitro and in silico screening studies. In the present study, half maximal inhibitory concentration (IC50) of BP-Cx-1 was established with a radioligand method and a range of IC50 values between 22.8 and 40.3 µg/ml were obtained for adenosine receptors A1, A2A and prostaglandin receptors EP2, IP (PGI2). IC50 for serotonin 5-HT1 and for glucocorticoid GR receptors were 3.0 µg/ml and 12.6 µg/ml, respectively, both being within the range of BP-Cx-1 concentrations achievable in in vivo models. Further, distribution of [3H] labelled BP-Cx-1 in NIH3T3 murine fibroblasts and MCF7/R carcinoma cells was studied with autoradiography. [3H]-BP-Cx-1 (visualized as silver grains produced by tritium beta particles) was mainly localized along the cell membrane, in the perinuclear region and in the nucleus, suggesting ability of BP-Cx-1 to enter cells and bind to membrane or cytosol receptors. In our experiment, we observed the effect of BP-Cx-1 on maturation of dendritic cells (DCs): downregulation of expression of the lipid-presentation molecule CD1a, co-stimulatory molecules CD80, CD83 and CD 40, decreased production of pro-inflammatory cytokines IL-4 and TNF-α and increased production of anti-inflammatory cytokine IL-10. It is hypothesized that [3H]-BP-Cx-1 detectable in the nucleus is part of the activated GR complex, known to be involved in regulation of transcription of genes responsible for the anti-inflammatory response. Based on IC50, cell distribution data and results of the experiment with DCs it is suggested that the in vivo effects of BP-Cx-1 are mediated via GR and 5-HT1 receptors thus promoting development of tolerogenic effector function in dendritic cells.

[Administration of Palonosetron and Phenotropil for Prophylaxis of the N-V-D Stage of Acute Radiation Syndrome].

Experiments on small (rats) and large (dogs) animals have shown that a sequential administration of Palonosetron and Phenotropil decreases the intensity of the main manifestations of the N-V-D stage of acute radiation syndrome. These data show the appropriateness of a combined administration of Palonosetron and Phenotropil to prevent a reduced work capacity in the individuals participating in elimination of the consequences of accidents associated with overexposure to radiation.

[Effect of losartan on acute renal failure induced by severe ethylene glycol poisoning in rats].

The effect of an angiotensin receptor II antagonist (losartan) on the model acute renal failure (ARF) induced by severe ethylene glycol poisoning at 2/3 LD50 has been studied in rats. It is established that losartan administration (20 mg/kg for 72 h) produces a significant (4-fold) increase in the animal death rate, which is associated with ARF transition to a decompensation stage. Pronounced changes in the qualitative and quantitative composition of diurnal diuresis, more than 8-fold increase in the creatinine level, and 18-fold increase in the blood urea have been observed. Thus, the administration of losartan to ethylene glycol poisoned rats causes more pronounced degeneration of proximal tubule epithelium and destruction of glomeruli. It is concluded that the use of losartan for the treatment of ARF is inexpedient.

[The experimental evaluation of antiradiation effectiveness of beta-estradiol on survival rates and bone marrow hemopoiesis of X-ray irradiated mice].

The study was aimed at evaluating the radioprotective effectiveness of beta-estradiol following its prophylactic administration in conditions of acute irradiation. Evaluation of the radioprotective efficiency was performed by studying the 30-day survival rate, life expectancy, the structure of irradiated mice death, the bone marrow hematopoiesis using the method of exogenous colony formation. The prophylactic use of beta-estradiol at doses of 20 and 40 mg/kg 5 days before irradiation has been established to protect the exposed mice against radiation death induced by X-rays at doses LD50-90/30, thus increasing their survival rate by 17-58%, and to favor the reduced expression of post radiation disorders of bone marrow hematopoiesis.

[Effect of indometofen on the survival and bone marrow hemopoiesis of mice exposed to acute external gamma- or X-ray irradiation].

The purpose of the study is evaluation of radioprotective effectiveness of indometofen at its prophylactic administration in conditions of acute irradiation. Evaluation of radioprotective efficiency was performed by studying the 30-day survival rate, life expectancy, structure of deathly irradiated mice, and bone marrow hemopoiesis using methods of endogenous and exogenous colony formation. The prophylactic application of indometofen at doses 30 mg/kg for 5 days before irradiation has been observed to protect mice against radiation death induced by gamma or X-ray exposures at doses LD(50-70/30), increasing their survival rate by 16-44%, and reduce severity of post radiation disorders of bone marrow hemopoiesis.

[Biogenic elements and sulfate reduction in a flooded oil carbonate stratum]. / Biogennye élementy i sul'fatreduktsiia v zavodniaemom neftianom karbonatnom plaste

Biogenous sulphate reduction and accumulation of secondary H2S were caused by the action of pumping waters with a low content of mineral elements on carbonate collectors with a high concentration of relict H2S during long periods of time. The amount of sulphates, phosphates, and ammonium nitrogen in water from layers of various mineralization is sufficient for active sulphate reduction. Sulphates and phosphates are eliminated from rocks of layers with diluted waters. The maximum increase of SO42- in waters was 1545 mg/litre, that of HPO42- was 0.34 mg/litre. The amount of ammonium decreases with mineralization of the layer waters, remaining within the range of 129-7 mg/litre. The content of CO2 and HCO3- increases in diluted waters to 197 and 695 mg/litre, respectively, correlating with biogenous processes. The highest number of sulphate reducing bacteria (dozens of thousands of the cells per ml) was found in water with mineralization of 19 g/litre. Curves for the content of SO42-, HPO42-, NH4+, and CO2 have a common maximum in waters of the Polaznensky deposit with a salinity of 62 g/litre.