The radioprotective efficacy of recombinant flagellin (FL) and interleukin-1 beta (IL-1) administered in combinations for preventive or therapeutic purposes was studied in experiments on white mongrel mice. The drugs were administered i.p. at doses of 1 mg/kg (FL) and 50 μg/kg (IL-1β). Simultaneous administration of the drugs in the early stages before irradiation was shown to be most efficacious in terms of 30-day survival of mice exposed to x-rays at a dose of 7.5 Gy (100% survival of mice vs. 53% survival in the control group, p < 0.01). Sequential administration of FL before exposure and IL-1β after exposure increased survival of the mice by 40% ( p < 0.05). The results indicated that combined use of biotechnological drugs for radioprotection was promising.
Research objective. To evaluate the radioprotective effectiveness of recombinant flagellin when used alone or in combination with interleukin-1 beta for prophylactic or therapeutic effect on animals. Materials and methods. The effect of hybrid flagellin FliC Salmonella typhimurium and human interleukin-1β (Institute of Highly Pure Biopreparations, Saint Petersburg, Russia) on the 30-day survival of male mice exposed to lethal doses of X-ray radiation was studied. Survival of irradiated animals was analyzed by Kaplan-Meier method. Results. The preventive use of flagellin had a protective effect on the 30-day survival of mice irradiated with lethal doses of X-rays. Compared with the irradiated control, the administration of flagellin (1 mg/kg or 2 mg/kg) prior to X-ray exposure (7.5 Gy, 8.0 Gy or 8.5 Gy) increased the animal survival rate to 67-87%. Complex preventive administration of flagellin (1 mg/kg) and interleukin-1 beta (50 μg/kg) provided a 100% survival rate of the irradiated mice. Separate use of drugs was also effective; 92.8% of mice survived when flagellin was administered prior to irradiation and interleukin after. Conclusion. Recombinant flagellin is a promising candidate product for designing new generation of domestic radiation countermeasures, including combinations with interleukin-1 beta.
Objective: to estimate the perfluorane adsorption capacity of the drugs belonging to different pharmacological groups. Materials and methods. The binding of perfluorane to 50 drugs at concentrations of 12.5 to 100 ^M was studied in vitro using equilibrium dialysis. Results. Interactions of ligands with the particles of perfluorane emulsion were found to be of three types. Type 1 substances were characterized by negative affinity to perfluorane; type 2 ligands acted indifferently with the emulsion; type 3 compounds were reversibly adsorbed with the particles of the blood substitute by the affinity constants ( Kaff) of 104 M-1. Conclusion. The perfluorane adsorption capacity is ambiguous and seems to depend on the properties of ligands. Type 3 interactions, which may lead to an increase in blood adsorption capacity and change in the pharmacokinet-ics of drugs used in combination with perfluorane, appear to be the most important. Key words: perfluorane, binding, drugs, drug interactions.
Objective: to estimate the perfluorane adsorption capacity of the drugs belonging to different pharmacological groups. Materials and methods. The binding of perfluorane to 50 drugs at concentrations of 12.5 to 100 ^M was studied in vitro using equilibrium dialysis. Results. Interactions of ligands with the particles of perfluorane emulsion were found to be of three types. Type 1 substances were characterized by negative affinity to perfluorane; type 2 ligands acted indifferently with the emulsion; type 3 compounds were reversibly adsorbed with the particles of the blood substitute by the affinity constants ( Kaff) of 104 M-1. Conclusion. The perfluorane adsorption capacity is ambiguous and seems to depend on the properties of ligands. Type 3 interactions, which may lead to an increase in blood adsorption capacity and change in the pharmacokinet-ics of drugs used in combination with perfluorane, appear to be the most important. Key words: perfluorane, binding, drugs, drug interactions.