What is oxidative stress?

Oxidative Stress: Definition, Mechanisms, and Health Implications

Oxidative stress is defined as an imbalance between the production of reactive oxygen species (ROS) and the body's ability to neutralize these reactive intermediates through antioxidant mechanisms, leading to potential cellular and tissue damage. 1

Core Mechanisms of Oxidative Stress

Oxidative stress involves several key processes:

1. Production of Reactive Oxygen Species (ROS):

   • Mitochondria are a major source of intracellular ROS 1
   • The NADPH oxidase system in phagocytes is another primary source 1
   • Environmental stressors (UV radiation, pollutants, heavy metals) and certain drugs can increase ROS production 2

2. Redox Imbalance:

   • When ROS production exceeds antioxidant capacity, oxidative damage occurs 3
   • This imbalance leads to two main outcomes: oxidative macromolecule damage and altered redox signaling pathways 1

3. Cellular Damage:

   • Oxidative stress causes damage to various cellular components:
     • Lipids: Formation of malondialdehyde, F2-isoprostanes, and advanced lipoxidation end products 1
     • Proteins: Creation of advanced oxidation protein products, carbonyl formation, and thiol oxidation 1
     • DNA: Formation of 8-hydroxy-2'-deoxyguanosine and other DNA adducts 1

Physiological and Pathological Roles

Physiological Functions

• ROS are needed for adequate cell function, including energy production by mitochondria 3
• ROS play important roles in cell signaling under normal conditions 2

Pathological Implications

Oxidative stress contributes to numerous health conditions:

1. Neurodegenerative Diseases:

   • Alzheimer's disease, Parkinson's disease, and Huntington's disease 4
   • The brain is particularly vulnerable due to high oxygen consumption and rich polyunsaturated fatty acid content 4

2. Cardiovascular Diseases:

   • Contributes to endothelial dysfunction, vascular inflammation, and atherosclerosis 1
   • Increases overall cardiovascular disease risk 1

3. Inflammatory Conditions:

   • Mental stress induces pro-inflammatory cytokine production (TNF-α, IL-6, IL-1β) 1
   • Neuroinflammation generates excessive ROS, causing oxidative damage to brain tissues 1

4. Other Conditions:

   • Cancer, diabetes, chronic kidney disease 1, 5
   • Aging processes 3

Measurement and Biomarkers

Oxidative stress can be measured through various biomarkers:

• 3-nitrotyrosine-positive proteins
• 8-hydroxy-2'-deoxyguanosine
• Malondialdehyde
• F2-isoprostanes
• Advanced oxidation protein products 1

Antioxidant Defense Systems

The body has several mechanisms to counteract oxidative stress:

1. Endogenous Antioxidants:

   • Enzymatic systems (superoxide dismutase, catalase, glutathione peroxidase)
   • Non-enzymatic molecules (glutathione, uric acid, coenzyme Q) 6

2. Exogenous Antioxidants:

   • Vitamin E (α-tocopherol): Most important lipid-soluble antioxidant that protects membrane lipids from peroxidation 1
   • Vitamin D: May play a role in reducing oxidative stress in certain conditions 1
   • Dietary antioxidants: Flavonoids and polyphenols from plant foods 2

Clinical Considerations

1. Therapeutic Approaches:

   • Enhancing endogenous antioxidant systems may be more effective than direct ROS scavengers 1
   • Targeted antioxidant therapies show promise for specific conditions 1
   • Anti-inflammatory strategies may help reduce oxidative stress 1

2. Dual Nature of Oxidative Stress:

   • While generally harmful, oxidative stress is sometimes exploited therapeutically, such as in cancer treatment 2
   • ROS can be both toxic byproducts leading to tissue damage and important signaling molecules 5

3. Limitations of Antioxidant Therapy:

   • Despite theoretical benefits, prevention by antioxidants has been mostly inefficient in clinical settings 3
   • Clinical trial outcomes with antioxidants have been inadequate despite promising preclinical studies 5

Understanding oxidative stress is crucial for developing effective strategies to prevent and treat various diseases where redox imbalance plays a significant pathophysiological role.