Biomedical Engineering Reference
In-Depth Information
2.4 Hydroxyl Radical (OH
)
Hydroxyl radicals are the most reactive of all ROS even though they have a short
half-life [
24
]. OH
is formed in biological systems from H
2
O
2
, as described pre-
viously. Due to its high reactivity, OH
reacts non-specifically with any cell
component (DNA, lipids, proteins, amino acids and sugars) causing loss of cell
integrity and function [
25
,
26
]. a-tocopherol effectively converts OH
by forming
stable tocopheroxyl radicals, which are then reduced by ascorbate and NADH/
NADPH-dependent reductase enzymes into phenol [
27
].
2.5 ROS Scavengers
To protect against ROS damage, cells produce antioxidant enzymes. Major
intracellular ROS scavengers include superoxide dismutase (SOD), glutathione
peroxidase (GSH-Px) and catalase [
9
]. SOD catalyzes the dismutation of super-
oxide into hydrogen peroxide, and GSH-Px removes H
2
O
2
by oxidizing reduced
glutathione (GSH) into glutathione disulfide (GS-SG, Eq.
9
). Catalase decom-
poses H
2
O
2
into H
2
O and O
2
(Eq.
10
). Antioxidant enzyme expression is altered
by a variety of factors, including angiotensin II, tumor necrosis factor-a (TNF-a),
interleukin-1b, and hydrogen peroxide [
28
-
31
].
2GSH
þ
H
2
O
2
!
GS
SG
þ
2H
2
O
ð
9
Þ
2H
2
O
2
!
2H
2
O
þ
O
2
ð
10
Þ
3 Reactive Species in Angiogenesis
A variety of ROS play critical roles in angiogenesis. Low dose ROS initiate
angiogenesis, often through physiologic ROS production in response to an applied
stimulus. However, externally applied ROS can also initiate angiogenesis. Once
the angiogenic process is underway, ROS act as second messengers in angiogenic
signal transduction pathways. While conflicting reports describe pro-and anti-
angiogenic effects of ROS in wound healing [
32
-
35
], ROS dose and timing as well
as cell redox state are critical to determining their cellular response [
36
].
3.1 ROS-Induced Initiation of Angiogenesis
ROS that initiate angiogenesis can come either from biological production by
adjacent cells or from sources external to the tissue. In wounds, leukocytes digest
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