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Medical Management of Acute Radiation Syndromes : Comparison of Antiradiation Vaccine and Antioxidants radioprotection potency. Maliev, Slava; Popov, Dmitri; Lisenkov, Nikolai Authors: AA(Russian Academy of Science), AB(Advanced Medical Technologies Affiliation: and Systems), AC(Moscow State Academy of Veterinary Medicine and) 38th COSPAR Scientific Assembly. Held 18-15 July 2010, in Bremen, Publication: Germany, p.4 00/2010 Publication Date: ADS Origin: Symposium F, session 23, paper number F23-0018-10 (Poster, Nr. FriComment: 326) Bibliographic Code: 2010cosp...38.3184M Title:

Abstract Introduction: This experimental study of biological effects of the Antiradiation Vaccine and Antioxidants which were used for prophylaxis and treatment of the Acute Radiation Syndromes caused by high doses of the low-LET radiation. An important role of Reactive Oxyden Species (Singlet oxygen, hydroxyl radicals, superoxide anions and bio-radicals)in development of the Acute Radiation Syndromes could be defined as a "central dogma" of radiobiology. Oxida-tion and damages of lipids, proteins, DNA, and RNA are playing active role in development of postradiation apoptosis. However, the therapeutic role of antioxidants in modification of a postradiation injury caused by high doses of radiation remains controversial.Previous stud-ies had revealed that antioxidants did not increase a survival rate of mammals with severe forms of the Acute Radiation Syndromes caused by High Doses of the low-LET radiation. The Antiradiation Vaccine(ARV) contains toxoid forms of the Radiation Toxins(RT) from the Specific Radiation Determinants Group (SRD). The RT SRD has toxic and antigenic prop-erties at the same time and stimulates a specific antibody elaboration and humoral response form activated acquired immune system. The blocking antiradiation antibodies induce an im-munologically specific effect and have inhibiting effects on radiation induced neuro-toxicity, vascular-toxicity,

gastrointestinal toxcity, hematopoietic toxicity, and radiation induced cytol-ysis of selected groups of cells that are sensitive to radiation. Methods and materials: Scheme of experiments: 1. Irradiated animals with development of Cerebrovascular ARS (CvARS), Cardiovascular ARS (Cr-ARS) Gastrointestinal ARS(GI-ARS), Hematopoietic ARS (H-ARS) -control -were treated with placebo administration. 2. Irradiated animals were treated with antioxidants prophylaxisis and treatment of Cv-ARS, CrSRS, GI-ARS, Hp-ARS forms of the ARS. 3. irradiated animals were treated with radioprotection by Antiradiation Vaccine against CV-ARS, Cr-ARS, GI -ARS, HpARS forms of the ARS. 4. Irradiated animals were treated with development of Cr ARS, Cv-ARS, GI -ARS and Hp -ARS forms of the ARS -Combined administration of the Antiradiation Vaccine and Antioxidants used for radiation protection and treatment. Equipment for irradiation: 60 Cobalt Facility : "Panorama", "Puma". Exposure rate: o.6 Gymin. During experiments, animals received the whole-body irradiation in a single dose. The radiation doses varied in a range from 7.5 Gy up to 10 Gy. These experiments were accomplished at the radio-biology department of Moscow State Academy of Veterinary Medicine and Biotechnology and Department of Scientific Research Institute of Nuclear Physics, Dubna, Russia. Radioprotectants: 1. Antioxidants : The Antioxidant mixture contained Coenzyme Q10, Vitamin A(retinol), Vitamin C(ascorbic acid), natural beta-carotene, d-alphatocopherol succinate, d-alpha tocopherol acetate. The antioxidants mixture was prepared in a powder form. Method of administration: oral administration by gavage. The doses of antioxidants varied from 100 mg/kg up to 500 mg/kg. 2. Placebo: Method of administration: oral ad-ministration by gavage. Five days daily before and after the whole-body gamma-irradiation. 3. Antiradiation Vaccine (ARV) contained toxoid (inactivated) forms of radiomimetics -Neu-rotoxins SRD-1; SRD-2; SRD-3 and Hematotoxins SRD-4. Method of administration ARV: intramuscular or subcutaneous,24 days before irradiation. Animals: 15 Sheep, 50 rabbits. Re-sults: The results of oral administration of antioxidants mixture provided before and after the whole-body high doses of gamma-irradiation at doses 10030 had demonstrated that survival rate was similar to placebo group -all animals died in first 5-10 days after irradiation. Ra-dioprotection activity did not depend on the doses of the antioxidants preparation and seam that high doses of antioxidants administered before and after irradiation were even harmful. Comparing to the placebo group, the group with antioxidants pretreatment and treatment had demonstrated a shorter life time after irradiation. The Group received the radioprotection with the Antiradiation Vaccine had demonstrated high survival rate -60% at severe form of CARS and up to 65-70% at severe forms of GI -ARS and H -ARS. Survival rates of irradiated animals after combined administration of the Antiradiation Vaccine (ARV) and Antioxidants were similar comparing to groups received the ARV-radioprotection at all forms of the ARS. Summary and conclusions: 1. Antioxidants (Per os) are not effective radioprotectants ther-apeutic agents at severe and extremely severe forms of Acute

Radiation Syndromes. 2. High doses of antioxidants, administered orally, 7 days before(dd)irradiation could be a factor which increased the lethality rate and decreased life time even comparing with the placebo group. 3. The Antiradiation Vaccine is an effective radioprotectant with 60-70% of survival rate at LD 10030 doses of irradiation and severe forms of the ARS. 4.Combined administration of the Antiradiation Vaccine (I/M) and antioxidants (Per os) could be useful even though the survival rates were similar to results with immunoprophylaxix by Antiradiation Vaccine alone. However, the group of irradiated animals with combined administration had demonstrated a better clinical picture and a shorter period of stage of recovery following after irradiation.