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

42 Free Radical Biomedicine: Principles, Clinical Correlations, and Methodologies Y. Robert Li
inhibiting or preventing the formation of ROS/RNS. For example, mono-O-methylated flavanols inhibit
NAD(P)H oxidases in vascular cells, leading to decreased superoxide production. Flavanols are phenolic
compounds found in plants (Section 2.17.4).
Sources of
ROS/RNS
inhibition
ROS/RNS
Scavenging
Antioxidants
Fig. (3.1). The three modes of action of antioxidants. Antioxidants may inhibit the ROS/RNS formation, scavenge
ROS/RNS, or repair the ROS/RNS-damaged biomolecules. See text (Section 1.1) for detailed description. ROS/RNS,
reactive oxygen and nitrogen species.
1.1.2. Scavenging of ROS/RNS
Many endogenous and exogenous antioxidants can directly scavenge ROS/RNS. Scavenging of ROS/RNS
can occur through enzyme catalyzed reactions. For example, superoxide dismutase catalyzes the
dismutation of superoxide to form hydrogen peroxide and molecular oxygen (Section 2.1). Non-enzymatic
antioxidants can also scavenge ROS/RNS through direct chemical reactions. These reactions can lead to the
formation of secondary free radical species from the non-enzymatic antioxidants. For example, the
antioxidant -tocopherol scavenges lipid peroxyl radical by reducing the lipid peroxyl radical to lipid
hydroperoxide (Section 2.3 of Chapter 2). In the reaction, the -tocopherol is oxidized to -tocopherol
radical. The -tocopherol radical is much less reactive than the lipid peroxyl radical.
1.1.3. Removal or Repair of the ROS/RNS-Induced Damage
ROS/RNS can cause damage or modifications to biomolecules, including proteins, lipids and nucleic acids.
Mammalian cells are equipped with various mechanisms to remove or repair the ROS/RNS-damaged or
modified biomolecules. For example, ROS/RNS oxidize methionine residues in proteins, yielding
methionine sulfoxide. The enzyme methionine sulfoxide reductase reduces the methionine sulfoxide in
proteins back to the normal methionine (Section 2.13). This is an important repairing mechanism for
oxidative protein damage in mammals. Mammalian cells also contain enzymes for repairing oxidative
damage of lipids and nucleic acids.
1.2. Classification Schemes of Antioxidants
In free radical biomedicine, antioxidants are classified in various ways (Table 3.1).
Damaged
Biomolecules
1.2.1. Endogenous and Exogenous Antioxidants
Based on sources, antioxidants are classified into endogenous and exogenous antioxidants. Endogenous
antioxidants refer to those naturally occurring in cells or tissues. These include superoxide dismutase, catalase
and the reduced form of glutathione, to name a few. On the other hand, those derived from dietary sources or
synthesized in laboratories are called exogenous antioxidants. Vitamins C and E, and various synthetic
mimetics of endogenous antioxidant enzymes are examples of exogenous antioxidants (Sections 2.17 and 2.18).
1.2.2. Intracellular and Extracellular Antioxidants
Based on locations, antioxidants are classified into intracellular and extracellular antioxidants. Intracellular
antioxidants are those present inside cells, such as copper, zinc superoxide dismutase. Extracellular
Repair