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Oxidative stress

Oxidative stress is a state of the cell in which the production of reactive oxygen species (ROS) exceeds the capacity of antioxidant defense systems - the result is damage to DNA, proteins, and cellular membranes, which is associated with accelerated aging, inflammation, and a wide range of chronic diseases.

 

Oxidative stress is a biochemical state characterized by an imbalance between the production of reactive oxygen species (ROS) and the cell's ability to neutralize them through antioxidant systems. ROS are highly reactive oxygen-containing molecules - most commonly superoxide anion (O₂⁻), hydrogen peroxide (H₂O₂), and hydroxyl radical (OH·). In small amounts, ROS are essential for cellular signaling; when their production exceeds antioxidant capacity, oxidative stress and cellular damage occur.

Oxidative stress is not a marginal phenomenon - research links it to inflammatory diseases, neurodegeneration, cardiovascular diseases, diabetes, cancer, and accelerated biological aging. At the same time, oxidative stress in mitochondria is one of the key factors directly influenced by photobiomodulation.

 

How oxidative stress arises

The main source of ROS in the body are mitochondria - as a byproduct of the respiratory chain during the production of ATP. Under physiological conditions, mitochondrial antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) neutralize these ROS. Oxidative stress occurs when this system becomes overloaded.

The main causes of excessive ROS production and the development of oxidative stress include:

  • Chronic inflammation - inflammatory cells (neutrophils, macrophages) produce ROS as part of the immune response; in long-term inflammation, this production becomes excessive
  • Impaired mitochondrial function - damaged or inefficient mitochondria leak more electrons from the respiratory chain, which increases the production of superoxide radicals
  • Intense physical exertion - increased metabolism during exercise generates more ROS than usual
  • Blockade of Cytochrome C Oxidase (CCO) by nitric oxide - when NO binds to CCO and blocks the respiratory chain, electrons accumulate and react with oxygen to form superoxides
  • Environmental factors - UV radiation, ionizing radiation, tobacco smoke, air pollution, toxins, industrial chemicals
  • Unbalanced diet - deficiency of antioxidants (vitamin C, E, polyphenols), excessive intake of processed fats and sugars
  • Chronic stress and cortisol - prolonged psychological stress increases baseline ROS production
  • Lack of sleep - during sleep, antioxidant capacities are restored; chronic sleep deprivation disrupts these processes

 

Health consequences of chronic oxidative stress

When oxidative stress persists long-term, ROS damage key biological molecules:

DNA damage - oxidative modifications of nucleotides lead to mutations and genomic instability. This mechanism is considered one of the main contributors to cancer and accelerated cellular aging.

Protein oxidation - ROS modify amino acid residues, leading to enzyme inactivation (including antioxidant enzymes), formation of protein aggregates, and disruption of cellular functions. This process is strongly present in neurodegenerative diseases.

Lipid peroxidation - ROS attack polyunsaturated fatty acids in cellular membranes, disrupting their structure and permeability. The result is impaired transport of substances into and out of cells.

Mitochondrial dysfunction - oxidative damage to mitochondrial DNA and respiratory chain enzymes reduces ATP production and creates a vicious cycle: less ATP means poorer restoration of antioxidant capacity, which leads to even greater oxidative stress.

Inflammation - ROS activate the transcription factor NF-κB, which triggers the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). Oxidative stress and inflammation reinforce each other in a chronic cycle.

 

Photobiomodulation and oxidative stress: biphasic effect

The relationship between photobiomodulation (red and NIR light therapy) and oxidative stress is one of the best-documented mechanisms of this therapy - and at the same time one of the most interesting, because it operates in a biphasic manner.

At low light doses (5 to 10 J/cm²):
Photobiomodulation reduces excessive ROS production in cells exposed to oxidative stress. Activation of Cytochrome C oxidase and increased ATP production provide the cell with energy to restore antioxidant enzymes. The result is a reduction in levels of oxidative damage (TBARS, MDA) and an increase in the activity of superoxide dismutase, catalase, and glutathione peroxidase. [R]

At higher light doses (20 to 50 J/cm²):
Photobiomodulation can temporarily increase ROS production in healthy cells without existing oxidative stress. This mild and short-term elevation of ROS acts as a signaling mechanism that stimulates cellular proliferation, activates antioxidant defense systems, and strengthens the immune response. It is a physiological hormetic response - the body reacts to mild stress by strengthening its protective capacities. [R]

This biphasic effect explains why proper dosing in photobiomodulation is critically important. A meta-analysis of systematic reviews confirmed that a single PBMT session can modulate redox metabolism - reducing oxidative damage and increasing enzymatic antioxidant activity after physical exertion. [R]

 

Antioxidants: the body's natural defense

The body has an extensive antioxidant defense system that effectively controls oxidative stress under physiological conditions:

Enzymatic antioxidants:

  • Superoxide dismutase (SOD) - converts superoxide anion into hydrogen peroxide
  • Catalase - breaks down hydrogen peroxide into water and oxygen
  • Glutathione peroxidase (GPx) - neutralizes peroxides with the help of glutathione

Non-enzymatic antioxidants:

  • Glutathione - the most important intracellular antioxidant; produced directly within cells
  • Melatonin - a powerful antioxidant produced directly in mitochondria; protects mitochondrial DNA and the respiratory chain from ROS
  • Vitamin C, vitamin E, polyphenols - obtained from the diet; neutralize ROS in various cellular compartments
  • Coenzyme Q10 - part of the respiratory chain; prevents electron leakage and the formation of superoxides

Photobiomodulation does not act as an external antioxidant, but stimulates the cell's own antioxidant capacity - it increases ATP production necessary for glutathione synthesis and antioxidant enzyme activity, and releases nitric oxide (NO), which inhibits lipid peroxidation.

 

Related terms

  • ROS (Reactive Oxygen Species - reactive oxygen radicals) - highly reactive oxygen molecules whose excessive production causes oxidative stress
  • Free radicals - atoms or molecules with an unpaired electron; most biologically relevant ROS are free radicals
  • Redox balance - the balance between oxidative and reductive processes in the cell; oxidative stress is its disruption
  • Antioxidants - molecules that neutralize ROS; enzymatic (SOD, catalase, GPx) and non-enzymatic (glutathione, melatonin, vitamin C, E)
  • Glutathione - the most important intracellular antioxidant; its synthesis depends on ATP availability
  • Melatonin - an antioxidant produced in mitochondria; its deficiency worsens antioxidant defense
  • Mitochondria - the main source of ROS in the cell and the primary site of oxidative stress damage
  • ATP - cellular energy essential for antioxidant enzyme function; its deficiency worsens defense against ROS
  • Photobiomodulation - red and NIR light therapy that reduces oxidative stress through a biphasic mechanism
  • Nitric oxide (NO) - a signaling molecule released during photobiomodulation; inhibits lipid peroxidation
  • NF-κB - a transcription factor activated by ROS; triggers inflammatory response; photobiomodulation modulates its activation
  • Hormesis - a biological phenomenon where a low dose of a stressor strengthens the organism’s defense capacity; describes the biphasic relationship between photobiomodulation and ROS

 

Frequently asked questions about oxidative stress

What is oxidative stress in simple terms?

Imagine the body has firefighting units (antioxidants) and small fires (free radicals). Small fires are normal and even train the firefighters - they are part of healthy functioning. Oxidative stress occurs when fires increase faster than the firefighting units can handle. The uncontrolled fire then damages cellular structures - DNA, membranes, proteins - and leads to chronic diseases.

How do I know if I have oxidative stress?

In everyday life, you cannot directly detect oxidative stress - its levels can be measured in the laboratory (oxidative markers such as MDA, TBARS, 8-OHdG, glutathione levels). Indirect signs include chronic fatigue despite sufficient sleep, slow wound healing, recurring inflammatory conditions, and accelerated signs of skin aging. However, these symptoms can have multiple causes - oxidative stress is one of them.

How does photobiomodulation reduce oxidative stress?

Red and NIR light activates Cytochrome C oxidase (CCO) in mitochondria, which increases ATP production. The cell thus has more energy for glutathione synthesis and for the function of antioxidant enzymes. At the same time, light releases nitric oxide (NO) from its binding to CCO - NO inhibits lipid peroxidation and inflammatory signaling. At low doses (5 to 10 J/cm²), the overall effect is a clear reduction in oxidative cellular damage. [R]

Is every free radical harmful?

No. Free radicals and ROS are biologically essential at physiological concentrations - they are part of the immune response (macrophages use them to destroy bacteria), cellular signaling, and hormetic adaptation to stress. The problem is exclusively their excessive production, which exceeds the body's antioxidant capacity. The goal is not the elimination of ROS, but the restoration of redox balance.

What is redox balance?

Redox balance (or redox homeostasis) describes a state in which oxidative and reductive processes in the cell are in equilibrium. Oxidative stress is a shift of this balance toward oxidation. Conversely, excessively strong antioxidant intervention (for example, high doses of antioxidants in supplements) can shift the balance in the opposite direction - which may disrupt the physiological signaling functions of ROS. That is why Mitochondriak® prefers approaches that restore natural balance (light, sleep, movement), rather than one-sided suppression of ROS.

What diet protects against oxidative stress?

Foods rich in antioxidants primarily include colorful vegetables and fruits (containing polyphenols, vitamin C), nuts and seeds (vitamin E, selenium), green tea (catechins), turmeric (curcumin), and dark chocolate (flavonoids). Equally important is limiting processed foods, industrial seed oils, and sugar - these directly promote oxidative stress. Diet is one of the levers, not the only one.

Can oxidative stress cause aging?

Oxidative stress is one of the key mechanisms of biological aging, but not the only one. The mitochondrial theory of aging suggests that the accumulation of oxidative damage to mitochondrial DNA over decades gradually reduces ATP production and increases leaking ROS - creating a self-amplifying cycle that worsens with age. Maintaining antioxidant capacity and mitochondrial function (through light, movement, sleep, and nutrition) is therefore one of the foundations of approaches focused on longevity.

 

Summary

Oxidative stress is an imbalance between the production of reactive oxygen species (ROS) and the antioxidant capacity of the cell. It damages DNA, proteins, and membranes, triggers inflammatory processes, and accelerates aging. Photobiomodulation (red and NIR light therapy) affects oxidative stress in a biphasic manner: at low doses it reduces it by restoring the cell’s antioxidant capacity and releasing nitric oxide; at higher doses it temporarily stimulates ROS as a hormetic signal to strengthen defense systems. Mitochondria are both the main source and the primary target of oxidative stress - their optimal function is the best prevention.

To learn more about how red light protects mitochondria, see the article How mitochondria produce energy (ATP) or visit the page of Mitochondriak® devices.

 

Scientific studies and sources

  • Photobiomodulation therapy on oxidative stress in muscle injury - systematic review, reduction of TBARS, increase in SOD, catalase, and GPx. PMC. 2017. PMC5623775
  • Can PBMT minimize exercise-induced oxidative stress? Systematic review and meta-analysis. Antioxidants (MDPI). 2022. doi.org/10.3390/antiox11091671
  • PBM in neuroinflammation - systematic review, reduction of oxidative stress and inflammatory cytokines in neurodegenerative diseases. PubMed. 2022. PMID: 36302150
  • Immunomodulatory effects of photobiomodulation - biphasic effect of PBM on ROS depending on dose. PMC. 2025. PMC11991943