Biomedical Engineering Reference
In-Depth Information
11
Oxidative Stress
Irfan Rahman
Department of Environmental Medicine, Lung Biology and Disease
Program, University of Rochester Medical Center, Rochester, NY, USA
I. INTRODUCTION
Reactive oxygen species (ROS) such as superoxide anion (O
2
-
) and the
hydroxyl radical (
OH) are highly unstable species with unpaired electrons,
capable of initiating oxidation. Biological systems are continuously exposed
to oxidants, either generated endogenously by metabolic reactions (e.g.,
from mitochondrial electron transport during respiration or during activa-
tion of phagocytes) or exogenously, such as air pollutants or cigarette
smoke. The lung exists in a high-oxygen environment and, together with
its large surface area and blood supply, is susceptible to injury mediated
by ROS. Production of ROS has been directly linked to oxidation of pro-
teins, DNA, and lipids, which may cause direct lung injury or induce a vari-
ety of cellular responses, through the generation of secondary metabolic
reactive species. ROS may alter remodeling of extracellular matrix and
blood vessels, stimulate mucus secretion, inactivate antiproteases, cause
apoptosis, and regulate cell proliferation (1,2) (Fig. 1). Alveolar repair
responses and immune modulation in the lung may also be influenced by
ROS. Furthermore, increased levels of ROS have been implicated in initiat-
ing inflammatory responses in the lungs through the activation of transcrip-
tion factors such as nuclear factor-kappaB (NF-
k
B) and activator protein-1
(AP-1), signal transduction, chromatin remodeling and gene expression of
pro-inflammatory mediators (3). It is proposed that ROS produced by
phagocytes that have been recruited to the sites of inflammation are a major
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