Reactive Oxygen Species (ROS) – Definition and Effects

What are Reactive Oxygen Species?

Reactive oxygen species (ROS) are chemically highly reactive molecules and molecular fragments that contain oxygen. They are generated as byproducts of normal cellular metabolism, particularly during energy production in the mitochondria. The most well-known ROS include the superoxide anion, hydrogen peroxide, and the highly reactive hydroxyl radical.

In small amounts, ROS serve important biological functions: they participate in immune defense, regulate cell signaling pathways, and play a role in cell division. However, when produced in excess or when the body´s antioxidant defenses are overwhelmed, a condition known as oxidative stress develops, which can damage cells, proteins, lipids, and DNA.

Sources and Formation

ROS are generated through both internal processes and external factors:

• Cellular respiration: During energy production in mitochondria, small amounts of electrons escape and react with oxygen to form superoxide anions.
• Immune response: Immune cells such as neutrophils and macrophages deliberately produce ROS to kill pathogens.
• Environmental factors: UV radiation, air pollution, cigarette smoke, alcohol, and ionizing radiation can significantly increase ROS production.
• Intense physical exercise: Physical exertion increases oxygen consumption and consequently ROS formation.
• Inflammatory processes: Chronic inflammation leads to sustained elevated ROS release.

Biological Functions

ROS are not inherently harmful. In controlled amounts, they fulfill essential roles in the body:

• Regulation of cell growth and programmed cell death (apoptosis)
• Activation of signaling molecules and transcription factors
• Contribution to innate immune defense (killing bacteria and viruses)
• Support of wound healing
• Involvement in hormone biosynthesis (e.g., thyroid hormones)

Oxidative Stress and Disease

When ROS production exceeds the capacity of the body´s antioxidant defense systems, oxidative stress occurs. This condition is associated with a wide range of diseases:

• Cardiovascular diseases: ROS promote the oxidation of LDL cholesterol and the development of atherosclerosis.
• Neurodegenerative diseases: Conditions such as Alzheimer's disease and Parkinson's disease are closely linked to oxidative stress in the brain.
• Diabetes mellitus: Elevated ROS levels can impair insulin sensitivity and promote complications.
• Cancer development: Oxidative DNA damage can cause mutations and contribute to tumor formation.
• Aging: The cumulative damage to cellular structures by ROS is considered one of the key drivers of biological aging.

Antioxidant Defense Mechanisms

The body has a sophisticated system to keep ROS in check:

Enzymatic Antioxidants

• Superoxide dismutase (SOD): Converts superoxide anions into hydrogen peroxide.
• Catalase: Breaks down hydrogen peroxide into water and oxygen.
• Glutathione peroxidase: Neutralizes peroxides using glutathione.

Non-enzymatic Antioxidants

• Vitamin C (ascorbic acid): A water-soluble antioxidant that directly scavenges free radicals.
• Vitamin E (tocopherol): A fat-soluble antioxidant that protects cell membranes from oxidation.
• Beta-carotene and other carotenoids: Plant pigments with antioxidant properties.
• Polyphenols: Secondary plant compounds found in fruits, vegetables, tea, and red wine.
• Glutathione: One of the most important intracellular antioxidants.

Diagnosis and Measurement

Measuring oxidative stress in clinical practice is challenging due to the short lifetime of ROS. Commonly used biomarkers include:

• Malondialdehyde (MDA): A breakdown product of oxidized fatty acids, measured in blood or urine.
• 8-Hydroxy-2-deoxyguanosine (8-OHdG): A marker of oxidative DNA damage.
• Oxidized LDL: An indicator of lipid peroxidation in the cardiovascular system.
• Glutathione status: The ratio of reduced to oxidized glutathione as a measure of antioxidant protection.

Therapeutic Approaches

Reducing oxidative stress can be supported through various measures:

• A balanced diet rich in fruits, vegetables, and whole grains (high antioxidant content)
• Avoiding smoking and excessive alcohol consumption
• Regular, moderate physical activity (promotes endogenous antioxidant production)
• Protection from excessive UV radiation
• Targeted supplementation with antioxidants (e.g., vitamin C, vitamin E) in confirmed deficiency -- always in consultation with a physician

It is important to note that excessive supplementation with antioxidants can be counterproductive, as ROS in physiological amounts fulfill important signaling functions.

References

1. Sies, H. (2015): Oxidative stress: a concept in redox biology and medicine. Redox Biology, 4, 180-183. DOI: 10.1016/j.redox.2015.01.002
2. Halliwell, B. & Gutteridge, J. M. C. (2015): Free Radicals in Biology and Medicine. 5th edition. Oxford University Press.
3. World Health Organization (WHO): Noncommunicable diseases -- oxidative stress and chronic disease prevention. Available at: https://www.who.int