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). Flagellin (0.2 mg/kg) was administrated once intraperitoneally before exposure of mice to low-intensive (10 mGy/min) γ-radiation at a dose of 12.65 Gy. The effect was evaluated in three groups: control, irradiated mice without of flagellin and with the administration flagellin 30 minutes before irradiation. Cytogenetic and cytotoxic effect in bone marrow was studied with micronucleus assay (OECD 474), in liver - with the original technique for cytome analysis of hepatocytes after fixation of liver pieces with 10% formalin, dissociation of cells with 50% KOH, staining with aceto-orcein and light green. The proportion of cells 2n, 2n + 2n, 4n, 4n + 4n, ≥8n and ≥8n + 8n was determined. Cytogenetic disorders were counted as cells with micronuclei, nuclear buds, and internuclear bridges. The ploidy index and nuclearity index were defined. RESULTS: In all studied groups of mice, the frequency of polychromatic bone marrow erythrocytes with micronuclei and hepatocytes with cytogenetic disorders did not exceed the background level. A decrease in the ploidy index of hepatocytes by 4.3 times was established 10 months after exposure to low-power ionizing radiation. In mice treated with flagellin before irradiation, the ploidy index was normalized to control. CONCLUSIONS: A decrease in the ploidy of hepatocytes was revealed 10 months after exposure to a high dose of low-power ionizing radiation, which may indicate the initiation of carcinogenesis. For the first time, a new aspect of the anti-radiation effect of promising radiation countermeasure flagellin was established and its hepatoprotective properties were determined in the long term after exposure to ionizing radiation.