Radiation Injuries Treatment
Development of Prophylaxis and Therapy Methods of Radiation Injuries by new Radioprotectors in Combination with Stimulation of Nonspecific Body Resistance
Tech Area / Field
- CHE-POL/Polymer Chemistry/Chemistry
- CHE-SYN/Basic and Synthetic Chemistry/Chemistry
3 Approved without Funding
The Scientific Centre of Radiation Medicine and Burns, Armenia, Yerevan
- Yerevan Institute "Plastpolymer", Armenia, Yerevan\nScientific Technological Center of Organic and Pharmaceutical Chemistry / Institute of Fine Organic Chemistry, Armenia, Yerevan
- University of Oxford / The Research Institute, UK, Oxford\nThomas Jefferson University / Jefferson Kimmel Cancer Center, USA, PA, Philadelphia\nThe Cleveland Clinic Foundation / Lerner Research Institute, USA, OH, Cleveland\nMcGill University Health Centre / Montreal General Hospital, Canada, QC, Montreal
Project summaryThe project aim is development of new methods of prophylactics and treatment of radiation injuries with application of new radioprotectors in combination with hypoxic stimulation of general non-specific resistency of an organism.
Searching of new effective means for prophylactics and treatment of radiation injuries, perfection of available methods is very actual issue in the sphere of radiation medicine. Study of radioprotective properties of chemical substances is carried out for protection of uninjured tissue of oncological patients who are exposed to intensive radiotherapy. The necessity to protect a human from ionizing radiation influence during liquidation of accident aftermaths on atomic plants and in case nuclear engagements is obvious. Development of appropriate radioprotective measures is very important while outer space exploration. More than 50 years has passed since the first chemical compounds that decrease affecting action of ionizing radiation on laboratory animals’ organism were discovered. Radioprotector properties of tens of thousands of preparations of different chemical nature were studied. It is revealed that the most effective radioprotectors are sulfur-containing substances and indolylalkylamines derivatives. The known drugs have a number of serious disadvantages – hyper toxicity, presence of adverse reactions, short-time action, variability of efficacy at different doses and types of ionizing radiation that significantly restrict their application capacities. There is not a unique and conventional conception on mechanisms of radioprotectors action in radiobiology. It is supposed that radioprotective action of sulfur-containing substances is realized at the expense of their intracellular accumulation in the radiosensitive tissues, whereas indolylalkylamines derivatives increase the radioresistance generally owing to development of hypoxia occurring in the result of their vasoconstrictive action.
One of the ways of handling the existing situation in case of absence of effective anti-radiation means, along with search of high-performance and safety radioprotectors is finding of new methods of prophylaxis and treatment of radiation injuries. In this project it is supposed:
- synthesis of new indolylalkylamines that contain fragments of 1,3-Diazaadamantane,
- obtainment of new radioprotector polymer systems;
- combination of radioprotective means with the factors that increase the general non-specific resistance of an organism, including natural radioresistance.
Toxicity, short-time action, low effectiveness significantly restricts the capabilities of indole derivatives application in practice. Introduction of preparations of lipophilic adamantane fragments into a molecule will decrease their toxicity, and will promote a bitter transportation of molecules through biological membranes. The other way of handling of the disadvantages is to include the active indole derivatives into polymer systems. There will be used non-toxic polymers as macromolecular systems for delivery of drug preparations with prolonged isolation of acting substance. Inclusion of radioprotector fragments into a content of non-toxic polymers will allow not only to prolong their action, but to decrease the used preparations’ doses, to reduce their toxicity and adverse reactions as well. Moreover, it is not excluded that having their own biological activity, polymers performing cooperative interactions with a radioprotector can significantly increase prophylactic and therapeutic efficacy of the preparations. The synthesized water soluble copolymers with optimal molecular mass will possess the so called “depot-effect” that is very important property in the prophylaxis and treatment of radiation injuries.
The leading role in effectiveness of protection from ionizing radiation undoubtedly belongs to radioprotector means. At the same time, a number of associated factors may have a significant meaning. In the frameworks of the present project it is supposed to use radioprotective means for prophylaxis of radiation injuries in the complex with measures of biological stimulation of general non-specific resistance of an organism. Increasing the level of non-specific resistance is based on directional stimulation of special type of adaptation reaction in an organism (activation and training reactions) that lead to stable increase of its protective, adaptive and compensational abilities. It is necessary to mention that in the result of non-specific resistance mechanisms activation endogenic background of an organism radioresistance increases as well (biologically active compounds of amines, thiols, other antioxidants that carry out protective functions with suppression of surplus caused by radiation injury peroxide oxidation products). Of special interest is hypoxic hypoxia. Adaptation to moderate periodical hypoxia in the condition of altitude chamber will not only increase organism stability to oxygen deficiency protecting it from stress and ischemic injuries, but will significantly decrease biological influence of ionizing radiation as well.
The results of the work regarding creation of new highly effective means and methods of prophylaxis and treatment of radiation injuries will have both important practical significance and scientific and theoretical interest for different braches of radiation medicine as well.
The achievement of project goals presupposes activity aimed at the solution of the main tasks: synthesis of new radioprotectors, including polymeric, study of physical and chemical properties; medical and biological research of radioprotective efficacy of synthesized preparations.
The establishment of characteristic interactions between structure, physical and chemical properties and medical and biological characteristics of perspective radioprotective means will allow realizing directive synthesis of indole derivatives and polymers with improved medical and biological properties.
Project methodology includes both well-known and developing by the project participants methods of synthesis of new radioprotective means and medical and biological assessments of their therapeutic and prophylactic effectiveness.
In accordance with ISTC goals the following tasks will be realized on performing the Project presented:
- Integration of the researchers from Armenia into the International scientific community;
- Re-orientation of the activity of scientists engaged previously in defense activity to solution of Public Health problems of persons having close contact with sources of ionizing radiation;
- Rendering assistance in solution of national and international problems related to human health while usage of atomic energy in modern life.
The goal of the project will be achieved by the joint efforts of a united team of highly professional scientists of the 3 leading research institutions of Armenia: Sector of Radiation Medicine and Burns of the CTOBR (WHO Collaborating Centre on Radiation Medicine and Burns); Institute of Fine Organic Chemistry by A. Mnjoyan NAS RA; Yerevan “Plastpolymer” Institute, which in accordance with their main activity profile have a positive experience in the frames of scientific and technical collaboration with ISTC in allied fields of chemical and technological and medical problems and possess a good command of methods for synthesis and processing of new materials and development of materials for medical application.
The International Science and Technology Center (ISTC) is an intergovernmental organization connecting scientists from Kazakhstan, Armenia, Tajikistan, Kyrgyzstan, and Georgia with their peers and research organizations in the EU, Japan, Republic of Korea, Norway and the United States.
ISTC facilitates international science projects and assists the global scientific and business community to source and engage with CIS and Georgian institutes that develop or possess an excellence of scientific know-how.