Preventive and therapeutic efficacy of recombinant flagellin in acute radiation injury

Abstract

The effect of prophylactic and therapeutic administration of recombinant flagellin on the survival rates of white outbred male mice exposed to sublethal doses of gamma radiation was studied. It has been established that the antiradiation activity of recombinant flagellin is most effectively manifested in its prophylactic administration 15–30 minutes before irradiation. A single intraperitoneal injection in a dose of 1000 µg/kg increases the survival rate of mice irradiated at a dose of 7 Gy by more than 50% (p<0,05). The administration of a dose exceeding 1000 mcg/kg has a pronounced toxic effect, which aggravates the severity of acute radiation injury and significantly increases the death of laboratory animals. The therapeutic administration of recombinant flagellin at a dose of 2, 20, 200 and 1000 µg/kg subcutaneously, 15–30 minutes after irradiation at a dose of 7 Gy, has a pronounced therapeutic effect. The survival rate of laboratory animals after administration of these doses of recombinant flagellin is from 39 to 50% in different groups. There were no significant differences between groups in the assessment of survival and average life expectancy. Consequently, with increasing or decreasing the dose of recombinant flagellin, its therapeutic efficacy does not change. With the prophylactic administration of recombinant flagellin at a dose of 1000 µg/kg subcutaneously 15–30 minutes before the irradiation of laboratory animals at a dose of 6,5 Gy, the number of colony forming units in the spleen is 20±3. This is almost four times the studied indicator (6±2 colony-forming units in the spleens, abs.), with therapeutic administration of recombinant flagellin at a dose of 20 µg/kg subcutaneously 15–30 minutes after irradiation at a dose of 7 Gy. The results confirm the promise of further research aimed at developing flagellin-containing chemical protection from radiation injury.

Keywords

recombinant flagellin / radioprotective efficacy / acute radiation injury / toll-like receptors / gamma radiation / survival / prophylactic and therapeutic administration of flagellin-containing agents

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