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УДК 619:615.849:633.1:591.145.2 DOI 10.33632/1998-698Х.2021-2-16-19
STUDY OF RADIOPROTECTIVE PROPERTIES OF DRUGS BASED ON E. COLI METABOLITES AND SUBSTANCES OF NATURAL ORIGIN
M.Yu. Gallyamova
FSBSI "Federal Center for Toxicological, Radiation and Biological Safety", 420075, Kazan Scientific town-2,
e-mail: [email protected]
Several series of experiments studied the preventive and therapeutic properties of preparations based on strains of E. coli "PL-6" microorganisms and products of their metabolism with the addition of natural hydroxides and aluminum hydrosilicates in acute radiation sickness of animals. We found that the use of drugs for both preventive and therapeutic purposes had a radioprotective effect, protecting from death from 60 to 80 % of animals with 100 % death of mice in the radiation control group. The greatest survival was achieved with the prophylactic use of compositions from a suspension of E. coli cells in a culture liquid with the addition of: 1) 1/10 of aluminum hydrosilicate; 2) 1/10 of 0.5 % formalin (survival rate of 80 % of fatally irradiated mice). A smaller radioprotective effect was achieved with the prophylactic and therapeutic use of drugs containing: 1) suspension of E. coli cells in a culture liquid with the addition of 1/10 of aluminum hydroxide; 2) a culture liquid with the addition of 1/10 of aluminum hydrosilicate; and 3) a culture liquid with the addition of 1/10 of aluminum hydroxide (survival rate of 60 % of irradiated animals). Preparations containing a suspension of E. coli cells in a culture liquid with the addition of: 1) 1/10 of aluminum hydro-silicate; 2) 1/10 of aluminum hydroxide during therapeutic use provided survival of 80 % of fatally irradiated mice; 3) preparations of E. coli cell suspension in a culture liquid with the addition of 1/10 of 0.5 % formalin; 4) culture liquid with the addition of 1/10 of aluminum hydrosilicate and 5) culture liquid with the addition of 1/10 of aluminum hydroxide protected 60 % offatally irradiated animals from radiation death. Suspension of E. coli cells in a culture liquid with the addition of 1/10 of aluminum hydrosilicate was administered to white mice on 10, 7, 5 and 3 days before lethal irradiation and 3, 5, 7 and 10 days after irradiation. The drug administered 10, 7, 5 and 3 days before and 3 and 5 days after irradiation protected up to 80 % of mice and applied 7 and 10 days after radiation expo-sure protected up to 60 % of mice. Research has shown that microbial preparations have radioprotective properties and can be used in the creation of radioprotective compositions.
Keywords: E. coli, metabolic products, natural minerals, radiation sickness, radiation sickness prevention, radiation sickness treatment.
Introduction. The purpose of research is the development of means of protection of farm animals from radiation damage. Surrounding human and animal wildlife is characterized by the concept of "technosphere" [1], this is due to contamination of biogenic waste chemical industry niches, products of nuclear fission of uranium and plutonium as a result of radiation incidents of previous years and others [2]. Mammalian organism responds to these conditions are all possible disturbances on celllevel system with various manifestations of depression and other allergic conditions, which requires a certain correcting [5, 8]. Previously, to enhance the body's defenses have used chemical agents. Currently more preferred substances of biological nature since they are less harmful to have no adverse effects [3, 4].
In this regard, the Department of Radiobiology of the Federal Center for Toxicological, Radiation and Biological Safety, within the framework of the established tasks, conducts screening studies of substances of biological nature that have immunostimulating, adaptogenic, immunomodulating, reactogenic, antitoxic and radioprotective actions and these studies are the next step [6, 7].
Materials and methods. The therapeutic and prophylactic properties based on formulations strain of microbial cells of E. coli "PL-6" and their metabolites radiation injury of animals was evaluated in three series of experiments.
Results and discussion. In the first series as models were used 60 white mice with body weight 18-20 g, separated according to the principle analogs into 12 groups of 5 animals in each group.
Microbial test animals administered a composition based on cell culture E. coli "PL-6", and their metabolic products with the addition of the various components: aluminum silicate (1st, 4th, 6th, and 9th group) aluminum hydroxide (2nd, 5th, 7th and 10th group) at the rate of 10 % by volume and 0.5 % formalin (3rd and 6th group). Formulations administered once sub-cutaneously to the inner thigh in a dose of 0.1 ml / head. Mice of the 11th and 12th groups served as
controls exposure and biological control (tab. 1).
In the second series of experiments, 130 white mice with similar body weight on the principle of analogues has been divided into 26 groups of 5 animals in each group.
The prophylactic and therapeutic effect of three types of drugs was studied on mice irradiated with a lethal dose (7.7 Gy) - suspension of E. coli cells in culture fluid with the addition of aluminum hydrosilicate at the rate of 10 % by volume, microbial polyantigen E. coli "PL-6" and anti-radiation treatment and prophylactic immunoglobulin. The test substances were administered to animals at a dose of 50 mg per 1 kg of live weight parenterally for 10 days (1st group), 7 days (2nd), 5 days (3rd) and 3 days (4th) before and after 3 days (5th), 5 days (6th), 7 days (7th) and 10 days (8 th) after irradiation (suspension of E. coli cells in the culture fluid); 10 days (9th group), 7 (10th), 5 (11th) and 3 (12th) before and after 3 (13th), 5 (14th), 7 (15th) and 10 (16th) days after irradiation (microbial polyantigen E. coli "PL-6") and 10 days (17th group), 7 (18th), 5 (19th ) and 3 (20th) before and 3 (21st), 5 (22nd), 7 (23rd) and 10 (24th) days after irradiation (anti-radiation immunoglobulin). Mice of the 25th and 26th groups served as radiation control and biological control (tab. 2). In the third series of experiments, formulations were tested on 20 mice № 1 and 4, with their therapeutic application twice after 1 and 5 days after lethal irradiation of mice. For this animal was formed 4 groups of 5 animals in each group. Formulations № 1 - suspension of E. coli cells in liquid culture with the addition of aluminum silicate (1st group) and № 4 - culture medium with the addition of aluminum silicate (group 2) was administered parenterally in the inner part of the thigh at a dose of 0.1 ml /goal. Animals of the 3rd and 4th group served as the control of radiation and biological control.
Modeling of acute radiation syndrome was performed by a single external gamma irradiation at a dose of 7, 7 Gy (LD 100).
The mice were maintained on a normal diet. The animals were clinically observed for 30 days, recording the dead and the survivors. Conclusion. The study found that both prophylactic and therapeutic use of preparations provided radioprotective effect, providing a 60-80 % survival of experimental animals with 100 % of mice death irradiation control group.
The highest survival rate was achieved for prophylactic use compositions № 1 and 3 (80 % survival of lethally irradiated mice). Smaller radioprotective effect was achieved in the prophylactic and therapeutic application of drugs № 2, 4 and 5 (60 % survival of irradiated animals).
Note: N is the number of animals.
Table 1 - Scheme of experience
Drug number The composition of the recipes Type of application N
1 Suspension of E. coli cells in the culture fluid with the addition of aluminum hydrosilicate at the rate of 10 % by volume Prevention 5
Treatment 5
2 Suspension of E. coli cells in the culture fluid with the addition of aluminum hydroxide at a rate of 10 % by volume Prevention 5
Treatment 5
3 Suspension of E. coli cells in the culture fluid with the addition of 0.5 % formalin at the rate of 10 % by volume Prevention 5
Treatment 5
4 Culture fluid with the addition of aluminum hydrosilicate at the rate of 10 % by volume Prevention 5
Treatment 5
5 Culture fluid with the addition of aluminum hydroxide at the rate of 10 % by volume Prevention 5
Treatment 5
Table 2 - Scheme of experience
№ Used drugs Time of the drug use N
Suspension of E. coli cells in culture fluid with the addition of aluminum hydrosilicate at a rate of 10 % by volume 10 days before 3 days later 5
1 7 days before 5 days later 5
5 days before 7 days later 5
3 days before 10 days later 5
10 days before 3 days later 5
2 Microbial polyantigen E. coli "PL-6" 7 days before 5 days later 5
5 days before 7 days later 5
3 days before 10 days later 5
10 days before 3 days later 5
3 Anti-radiation treatment prophylactic immunoglobulin 7 days before 5 days later 5
5 days before 7 days later 5
3 days before 10 days later 5
Note: N is the number of animals.
Drugs № 1 and 2 in the therapeutic use of the compositions showed high efficiency, ensuringthe survival of 80 % of lethally irradiated mice.
Less pronounced therapeutic effect was achieved using preparations № 3 - suspension of E. coli cells with the addition of formalin, № 4 -culture broth with addition of aluminum silicate and № 5 - the culture broth with addition of aluminum hydroxide with the use of metabolic products of E. coli - protection against radiation death of 60 % of lethally irradiated animals.
It should be noted that the drug № 1 made on the basis of a mixture of E. coli cells and the culture medium with the addition of a solution of aluminum silicate with both applications, provided the maximum radioprotective effect, protecting from death 80 % of lethally irradiated animals. Prophylactic use of the drug № 3 on the basis of cell biomass with the addition of formalin also noted a high radioprotective effect (80 %).
Preparation № 2 based on a mixture of bacteria and the culture medium with the addition
of aluminum hydroxide at therapeutic application also provided maximum radioprotective effect, keeping from death 80 % of the animals.
The studies were selected promising formulation - suspension of E. coli cells in liquid culture with the addition of aluminum silicate having preventive and curative properties and protects 80 % of animals in all embodiments of its use.
The action of this formulation was tested on white mice, prevented 10, 7, 5 and three days before lethal exposure and 3, 5, 7 and 10 days after irradiation in comparison with the well-known drugs - microbial polyantigen and antiradiation treatment and prophylactic immu-noglobulin.
It was found that the suspension of E. coli cells, administering to the animal a prophylactically for 10, 7, 5 and 3 days protected from radiation death 80 % of the animals. The same drug administered at 3 and 5 days after irradiation protected the mice, and 80 % after 7 days and 10 - 60 % of the animals. It was
shown that the preparation of 1 № therapeutic effect was not inferior to the control antiradiation therapeutic and prophylactic immunoglobulin, but was less (20 %) active when its therapeutic use.
Of the tested drugs for therapeutic purposes № 1 and 4 in the third series of experiments showed the highest activity formulation № 4 (a metabolite of bacteria of the strain E. coli "PL-6" with the addition of
aluminum silicate at 10 % by volume), which is protected from radiation death 80 % of the animals; 60 % activity possessed preparation № 1 at 100 % death of the animals exposure control.
Studies have shown that compositions based on the microbial cells of the strain E. coli "PL-6" and their metabolites have radioprotective properties when prophylactic and therapeutic application and may be used in the development of radioprotective agents.
References
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5. Titov, A.S. Substances of microbial origin to enhance the immune reactivity of animals // A.S. Titov, R.N. Nizamov, D.T.Sharifullina, R.V. Nefedova, K.N. Vagin, G.I. Rakhmatullina // Collection of materials of the International scientific-practical conference dedicated to the 50th anniversary of the «Federal Center for Toxicological, Radiation and Biological Safety». - Kazan, 2010. - P. 339.
6. Sharifullina, D.T. The technology for producing radioprotective compositions of metabolic products E. coli / D.T. Sharifullina, A.S. Titov, R.N. Nizamov // "Bulletin" of the Russian Military Medical Academy, St. Petersburg, 2015. - № 3. - P. 165.
7. Sharifullina, D.T. Obtaining radioprotective drugs based on products of microbial metabolism and natural minerals / D.T. Sharifullina, R.N. Nizamov, G.V. Konyukhov, K.N. Vagin, A.S. Titov, M.M. Shakurov // Actual problems of veterinary medicine: Materials of a scientific-practical conference dedicated to the 90th birthday of Professor V.A. Kirshin. - Kazan, 2018 - P. 107.
8. Sharifullina, D.T. The use of substances of microbial origin to increase the radioresistance of animals / D.T. Sharifullina, R.N. Nizamov, G.V. Konyukhov, R.V. Nefedova, K.N. Vagin, G.I. Rakhmatullina // Materials of the International scientific-practical conference "Modern biosafety and biosecurity systems in veterinary medicine", 2010 - P. 314.
УДК 619:616.9:578.74 Б01 10.33632/1998-698Х.2021-2-19-24
СЕРОИММУНОЛОГИЧЕСКИЙ МОНИТОРИНГ НА ХЛАМИДИОЗ НЕБЛАГОПОЛУЧНЫХ СВИНОВОДЧЕСКИХ ХОЗЯЙСТВ ПРИВОЛЖСКОГО ФЕДЕРАЛЬНОГО ОКРУГА
В.В. Евстифеев - доктор биологических наук, доцент, Ф.М. Хусаинов - доктор ветеринарных наук, Г.И. Хусаинова - кандидат биологических наук, И.Р. Акбашев, С.И. Яковлев, Р.З. Хамидуллина
