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Antioxidant System and Bronchial Asthma

#G-1643


The Study of Antioxidant Defense System Role in Bronchial Asthma: Development of Electrochemical Methods for the Evaluation of Antioxidant System Status

Tech Area / Field

  • BIO-CHM/Biochemistry/Biotechnology
  • CHE-ANL/Analytical Chemistry/Chemistry
  • ENV-EHS/Environmental Health and Safety/Environment
  • ENV-MIN/Monitoring and Instrumentation/Environment
  • MED-DIS/Disease Surveillance/Medicine

Status
3 Approved without Funding

Registration date
21.05.2008

Leading Institute
Tbilisi State University / Institute of Physics (Ge), Georgia, Tbilisi

Supporting institutes

  • Ural State Economic University, Russia, Sverdlovsk reg., Ekaterinburg

Collaborators

  • Queen Mary, University of London / Interdisciplinary Centre in Biomedical Materials, UK, London\nTETRAD Technologies Group, Inc., USA, VA, Richmond

Project summary

A large variety of anthropogenic and natural emission sources contribute to pollution of the environment. The environmental contamination has become a serious health concern. Epidemiological studies show that the particulate matter (PM), containing toxic metals, chemical compounds, and materials of biological origin could be the source of respiratory and cardiovascular diseases. Many of the mentioned pollutants exist in nanosized form, which makes it extremely toxic. Taking into consideration the complexity of urban air particles, in real life conditions, it is difficult to separately characterize the health risks associated with some particular pollutants.

Our approach is addressed to assessment of the combined effects of PM and other pollutants on asthma risk at the mining-source emitting mining dust PM representing a dominant form of urban air pollution at the Chiatura city location. The area of Chiatura containing manganese ores is known as one of the most metal-polluted zones of Georgia. Daily, Chiatura district is characterized by substantially increased numbers of inpiduals suffering from adverse type of the respiratory tract inflammations, including bronchitis and occupational asthma. Asthma is a complex chronic inflammatory disease of airways. Despite increasing knowledge about mechanisms, pathophysiology and treatment in asthma, it should be realized that the problem of asthma remains far from being solved.

This project is based upon the hypothesis that an oxidative stress plays a crucial role in the pathogenesis of asthma. Activated inflammatory cells produce reactive oxygen species (ROS) and when free radicals scavenging antioxidant systems are overwhelmed, inflammation, hypersensitivity, and autoimmune conditions may take place. The important role in cell antioxidant capacity, with the exception of specific cellular antioxidants, belongs to peptides and proteins, which can be easily oxidized. Their composition includes thiol-containing amino acid cysteine. These peptides define the redox potential of cells and tissues. As concern thiol-containing proteins, various stresses and pathological conditions lead to reversible oxidative modifications of thiol groups, generating an increase of disulfide bonds. Such modifications change the membrane permeability, its adhesive property, and influence cytoskeleton organization, enzymatic activity and cell proliferation.

The main experiments are specifically designed to elucidate the antioxidant defense status and redox potential in blood cells and plasma of patients suffering from two types of occupational asthma (OA): immunological, characterized by the overproduction of specific antibodies IgE and non-immunological, for which a specific immune mechanism has not been identified, will be used to test this hypothesis. The experimental technique will include modern biochemical approaches and instrumentation, which were used in terms of the ISTC project G-349 to study redox environment and antioxidant imbalance caused by low dose long-term action of some heavy metals on human epithelial cells in vitro, and inexpensive commercial equipment and new readily available electrochemical methods and sensors for rapid assessment of the antioxidant activity and thiol-disulfide ratio in biological systems. Large sensitivity, high selectivity and rapid acquisition of results, which are ensured by electrochemical methods, provide the possibility to adapt the relatively simple instruments developed in terms of ISTC Projects NN342 and 2132, and use it as prototypes for fulfillment of the proposed project. The established methods of organism oxidative stress determination, assessment of antioxidant activity in various biological samples, determination of reduced and oxidized thiol forms and microelements are laborious, non-operative, demand high-qualified staff and application of expensive equipment. Of great importance is the creation of commercial equipment and working out new available methods providing pilot evaluation oxidant/antioxidant balance of biological system.

Aims of the proposed project are:

  1. To elucidate the role of the integral antioxidant defense system and its inpidual components in the etiology of occupational asthma and find the correlation, which can be used for the risk-factor estimation, early diagnosis and the development of novel therapeutic strategies.
  2. To adapt electrochemical sensors, instruments, software, measurement techniques of antioxidant activity (AOA), SH/S-S ratio (TDR) in biological liquids, worked out in the frames of ISTC Project 2132, for express diagnostics in clinical conditions.

Here proposed multidisciplinary research relies on the scientists involved in the study to provide experience and expertise in fields of biochemistry, electrochemistry, cell biology, immunology and biophysics.

Expected achievements are:

  • The new information in the etiology of occupational asthma, specifically the roles of the antioxidant defense system, what could be the basis of the effective therapy.
  • The development of new readily available methods and instrument prototypes for rapid assessment of the antioxidant activity (AOA) and thiol-disulfide ratio (TDR) in biological systems, which in conjunction with the former achievement will allow one to realistically assess and elucidate the importance of antioxidant systems in the therapy of bronchial asthma, and the elaborated correlation may be used as hallmarks of effective therapy.

The successful fulfillment of the project tasks is based on the:
  • High professional skills of scientists (which are confirmed by a large number of their frequently cited publications), physicians and engineers, who will be involved in the project work.
  • Wide opportunities and the experience in estimation of the oxidative stress by modern methods (Andronikashvili Institute of Physics, Georgia, awarded by ISTC grant G-349).
  • A large experience in development of electrochemical measurement means (USUE).
  • The results of preliminary analysis of antioxidant activity, thiol-disulfide ratio in real biological materials (blood and its fractions) using electrochemical methods (Central Clinical Hospital SB of RAS and USUE).
  • A long-term experienced and competent foreign collaborators.

The project serves to ISTC goals and objectives in the integration of former weapon scientists from Georgia and Russia into the international scientific community, fosterage self-sustaining civilian activities of CIS scientists (in this case, environmental health research). Project supports applied research and development of new technologies in medical sphere.

The project collaboration facilitates the development of the market economy and satisfies civil requirements since the international market badly needs equipment for quick prenosological diagnostics, preventive therapy, and evaluation of the condition of patients, and the choice of appropriate therapeutic treatment during emergencies. The successful commercialization of the equipment and the sensors, which were developed under ISTC Projects NN342 and 2132, gives a good outlook for the similar successful commercialization of results obtained in terms of the proposed project.

The proposed research co-operation with foreign collaborators will include knowledge transfer, joint workshops and meetings, and technical monitoring of the project.


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