Free Radical Biomedicine: Principles, Clinical ... - Bentham Science

Antioxidants Free Radical Biomedicine: Principles, Clinical Correlations, and Methodologies 41
2.13. Methionine Sulfoxide Reductase
2.14. Paraoxonase
2.15. Other Protein Antioxidants
2.16. Other Non-protein Antioxidants Synthesized by Cells
2.17. Non-protein Antioxidants Derived from the Diet
2.18. Synthetic Non-protein Antioxidants
3. MOLECULAR REGULATION OF ANTIOXIDANTS
3.1. Antioxidant Response Element (ARE) and Nrf2
3.2. Other Transcription Factors
3.3. Chemical Inducibility of Antioxidants and Chemoprotection
4. ANTIOXIDANT-BASED INTERVENTION
4.1. Overall Strategies
4.2. Animal Studies
4.3. Human Studies
5. REFERENCES
1. OVERVIEW
As stated in Chapter 2, free radicals and related reactive species, especially reactive oxygen and nitrogen
species (ROS/RNS) are able to cause damage to biomolecules, leading to cell and tissue injury in mammals,
including humans. Thus, a number of endogenous antioxidant defenses have been evolved in mammals to
protect against the damage caused by ROS/RNS. In addition, a variety of exogenous compounds from natural
sources, including foods exhibit antioxidant properties in biological systems. This chapter describes the various
types of endogenous antioxidants in mammals as well as exogenous antioxidant compounds frequently
encountered in free radical biomedicine. It should be borne in mind that antioxidant enzymes or proteins are
widely distributed in various animal species, microorganisms, as well as plants. This book focuses on the
discussion of knowledge on antioxidants obtained from studies in mammalian species, including humans
though knowledge obtained from studies in lower organisms is also of critical importance.
1.1. Defining Antioxidants
The term antioxidant is frequently used in biomedicine, and has been defined in various ways in the
literature. One way to define the term is that antioxidant is any substance that can prevent, reduce or repair
the ROS/RNS-induced damage of a target biomolecule. There are several potential modes of action by
which antioxidants protect biomolecules from ROS/RNS-induced damage. Fig. (3.1) illustrates these
potential modes of antioxidant protection.
1.1.1. Inhibition of ROS/RNS Formation
ROS/RNS are produced by a number of cellular sources, including mitochondrial electron transport chain
and NAD(P)H oxidases (also known as NOX enzymes). Antioxidants may act on these cellular sources,