Oxidative stress

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Overview

Illustration of free radical toxicity.

Oxidative stress refers to an imbalance between the production of reactive oxygen species (ROS) and the body's ability to detoxify these reactive intermediates or to repair the resulting damage. It is a significant factor in the pathogenesis of various diseases and aging processes.

Mechanism

Oxidative stress occurs when there is an excess of free radicals, which are unstable molecules that can damage cellular components such as lipids, proteins, and DNA. The body uses antioxidants to neutralize these free radicals, but when the production of ROS exceeds the capacity of antioxidant defenses, oxidative stress ensues.

Sources of Reactive Oxygen Species

ROS are generated from both endogenous and exogenous sources. Endogenous sources include mitochondrial respiration, peroxisomes, and inflammatory cell activation. Exogenous sources include pollution, radiation, cigarette smoke, and certain drugs.

Biological Impact

Oxidative stress can lead to cellular damage, contributing to the development of various diseases such as cardiovascular disease, neurodegenerative disorders, cancer, and diabetes. It also plays a role in the aging process.

Cellular Damage

- Lipid Peroxidation: ROS can attack lipids in cell membranes, leading to loss of membrane integrity and cell death. - Protein Oxidation: Oxidative modification of proteins can result in loss of enzyme activity and structural damage. - DNA Damage: ROS can cause mutations by damaging the DNA, potentially leading to cancer.

Defense Mechanisms

The body employs several antioxidant defenses to mitigate oxidative stress:

- Enzymatic Antioxidants: These include superoxide dismutase, catalase, and glutathione peroxidase. - Non-Enzymatic Antioxidants: These include vitamin C, vitamin E, and glutathione.

Clinical Significance

Understanding oxidative stress is crucial for developing therapeutic strategies to combat diseases associated with it. Antioxidant therapy is an area of active research, aiming to enhance the body's natural defenses or to provide exogenous antioxidants.

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Contributors: Prab R. Tumpati, MD