Antioxidants and Oxidative Stress in Exercise
Sources of Oxidative Stress
- Uncoupling of the electron transport chain: 2-5% of the total electron flux escapes the respiratory chain to make O2-. Exercise increases ATP demand. O2 uptake can increase 20-fold. O2 flux through active muscle may increase 100-fold. So there is an increased possibility.
- Ischemia-reperfusion: Intense exercise can lead to tissue hypoxia. Hypoxia promotes an excess of electron donors, NADH. Xanthine oxidase. After a period of ischemia, an increased neutrophil infiltration is experienced.
- Inflammation by neutrophils: Muscle damage from exercise can cause inflammation by neutrophils, which release O2-.
- From other ROS (Haber-Weiss reaction): Less reactive O2- and H2O2 might create more reactive OH radicals.
- Hemoglobin/myoglobin autoxidation: Transition metal-containing proteins catalyze the formation of new radicals.
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Lipid peroxidation: A free radical steals an electron from a lipid in the cell membrane, leading to cell damage.
- Initiation: LH + OH- -> L- + H2O
- Propagation: L- + O2 -> LOO-
- LOO- + LH -> LOOH + L-
- Branching: LOOH + Mn+ -> RO- + OH- + Mn+1
- Termination: 2L -> LL
- L- + LOO- -> LOOL
- Autoxidation of catecholamines: During exercise, increased plasma levels of catecholamines (noradrenaline, dopamine) are observed. These can be autoxidated, which generates O2-.
Methods for Detection of Oxidative Stress
- Electron paramagnetic resonance: detection of radicals
- Detection of products from lipid peroxidation (MDA)
- Detection of DNA oxidation products (Thymine glycerol)
- Exhaled pentane (indicator of lipid oxidation)
Prevention of Oxidative Stress
- Prevention is impossible.
- There are antioxidants and antioxidant enzymes.
- Antioxidants: Vitamin C, Vitamin E, Carotenoids, GSH, and Q10
- Enzymes: superoxide dismutase, catalase, and glutathione peroxidase
Antioxidants scavenge free radicals by donating e- or H+.
Supplementation of Antioxidants
Supplementation of antioxidants lowers lipid peroxidation at rest and after exercise. But it doesn’t prevent the increase in oxidative stress:
- Vitamin E does not decrease neutrophil infiltration after exercise.
- Antioxidant supplementation does not decrease blood oxidative stress in relation to eccentric exercise.
- Beta-carotene supplements increase the incidence of lung cancer in the population.
Are Reactive Oxygen Species (ROS) Beneficial?
ROS and Reactive Nitrogen Species (RNS) are essential in cellular development and optimal function. Cells have evolved strategies to use ROS and RNS as biological stimuli. They may act as subcellular messengers in signaling processes and modulate enzyme and gene activation.
- Example: Role in the action of neutrophils
- Example: Induction of molecular mediators of insulin sensitivity and antioxidant defense
Neutrophils play a role in the innate immune system and produce O2- by the action of NADPH oxidase as part of the defense mechanism. Antioxidants prevent the health-promoting effect of physical exercise in humans.
Antioxidants prevent the induction of molecular mediators of insulin sensitivity and antioxidant defense by physical exercise.
Vitamin C and E hamper cellular adaptation to endurance training: COX4 (important for improving muscular endurance).
Epigenetics and Exercise
- DNA methylation
- Histone modification
- RNA interference
One genome can give rise to many different epigenomes. The epigenome determines the phenotype.
Methylation is the clustering of genes. If genes spread apart (hypomethylation), the genes can be expressed.
Exercise hypomethylates PGC1-alpha, PDK4, and PPAR-gamma (mitochondrial biogenesis).
So exercise gives good stress, eustress.
High L3MBTL1 expression is associated with less aggressive tumors and better survival outcomes.
Even in breast cancer patients who exercised, an increased hypomethylation of important genes associated with overall survival was experienced.