Use of botanical products such as exogenous antioxidants has gained considerable momentum in the last few years in therapy of human degenerative diseases. Among these antioxidants, tumeric, neem, guggul, alpha-tocopherol, Beta-carotene, and ascorbic acid have been shown to have a special relevance in maintaining the redox equilibrium in various cell types, including those of the nervous system. They have a strong commercial potential as dietary supplements or as potential pharmaceutical agents in the treatment of various human degenerative diseases. In Phase I of the project, our aim is to develop cell free in vitro assay systems for the measurement of the biological activities of these compounds, using biological molecules present in their free form as targets of reactive oxygen species (ROS). In the development of these methods, we will take into account the critical factors that may influence the results, for example: (a) different types of ROS; (b) different systems for the generation of these ROS; (c) different molecular targets of ROS, and (d) different methods for the measurements of the molecular lesions produced by the ROS. In Phase II of the proposed project, we will optimize assay systems in which the target molecule is present as an integral part of the cell (intact-cell systems). The intact-cell systems will use functional neurons and astrocytes in which the effects of ROS and antioxidants will be measured by their effects on the structural integrity of the mitochondrial DNA. Also, in Phase Il, we will develop an approach for assigning antioxidant indices to mixtures of antioxidants, using a minimum number of different assays.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
4R44NS043948-02
Application #
6798944
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (10))
Program Officer
Murphy, Diane
Project Start
2002-06-01
Project End
2005-07-31
Budget Start
2003-09-15
Budget End
2004-07-31
Support Year
2
Fiscal Year
2003
Total Cost
$468,618
Indirect Cost
Name
American Biotechnology Research Corp
Department
Type
DUNS #
City
Schaumburg
State
IL
Country
United States
Zip Code
60173