Oxidative stress

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As oxidative stress refers to a metabolic condition, border at which the physiological extent amount of reactive oxygen species (ROS - reactive oxygen species ) is formed or is present. These reactive oxygen compounds arise in the course of metabolic processes of the mitochondrial electron transport chain and cytochrome P 450 oxidases . These are the superoxide anion radical O 2 · - , hydrogen peroxide (H 2 O 2 ) and the hydroxyl radical · OH. Helmut Sies is considered to be the inventor of the term oxidative stress in 1985 .

Normal cells in the organism maintain their ability to neutralize reducing or oxidizing substances by producing and storing oxidizing or reducing substances. An imbalance between these pools that overwhelms the normal repair and detoxification function of a cell and can consequently lead to damage to all cellular and extracellular macromolecules is known as oxidative stress .

Effects

The consequences of high-grade oxidative stress include lipid peroxidation - which ultimately means that cells have to use more energy to stabilize their membrane potential - protein oxidation and DNA damage . These three processes are considered to be one of the causes of the aging process and a lower life expectancy . In contrast, low-grade or intermittent exposure to oxidative stress is beneficial to health and life-prolonging. This non-linear dose-effect relationship (i.e. low-dose = healthy, but high-dose = disease-causing) is known as " mitohormesis ".

Protection systems

Oxidative stress, antioxidants and protective enzymes

Cells and tissues have various protective mechanisms against oxidative stress available:

  1. Antioxidative protection system - enzymatic and non-enzymatic radical scavengers and antioxidants
  2. Secondary protection - repair mechanisms of the DNA and regulated breakdown of proteins (turnover)

Free radicals

Free radicals are formed by the respiratory chain , which lead to damage to the mitochondrial DNA (mtDNA). The cause is the close spatial relationship.

The net reaction in the respiratory chain of the cells is the exergonic reaction of oxygen with hydrogen ions to form water. Despite extensive protective mechanisms, this process is incomplete in around two percent of cases, as only one hydrogen atom combines with one oxygen atom and continues to react to form reactive oxygen compounds.

Role in the development of diseases

Despite numerous correlations between oxidative stress and various disease states, only a few connections could be proven. One possible connection is the destruction of mitochondria , microfilaments and proteins that lose their function due to the oxidation process. This leads to a functional impairment of the normal metabolic processes and changes in cells.

However, there is no evidence-based therapy based on the treatment of oxidative stress. Rather, the opposite is true: Several meta-analyzes came to the conclusion that the administration of antioxidants (especially beta-carotene , vitamin A and vitamin E ) counteracting oxidative stress promotes the development of diseases in humans, including cancer.

More recently, the influence of reactive oxygen species on the development of oxidative stress, especially with regard to neurodegenerative diseases such as stroke, Parkinson's disease , Alzheimer's disease, Huntington 's disease or amyotrophic lateral sclerosis (ALS), has been investigated. In this context, many studies, especially in Parkinson's disease, which is characterized by the loss of dopaminergic nigrostriatal neurons in the basal ganglia , point to an excess of free oxygen radicals with iron participation and to the oxidative stress generated as a result with a damaging transformation physiologically occurring in the substantia nigra Proteins (e.g. α-synuclein ). Signs of increased oxidative stress can also be detected in diabetic neuropathy . A genesis of oxidative stress after irradiation or also through hypoxia or hyperoxia and the resulting benefit of neurodegenerative diseases is also discussed . Certain cardiovascular diseases such as B. atherosclerosis or coronary heart disease could be caused by oxidative stress, since the oxidation of the LDL in the endothelium is regarded as a preliminary stage of plaque formation. It is currently generally assumed that factors that trigger or promote illness are responsible for the predominance of oxidative stress-generating substances over detoxification mechanisms (see below).

therapy

In a variety of studies, no benefit in humans could of antioxidants containing supplements are detected. On the contrary, many meta-analyzes indicate the harmfulness of an unfounded, broad intake of antioxidants and vitamins, including increased mortality. One reason for this seems to be that reactive oxygen species are not only dangerous waste products of a cell, but that the same oxygen species in low concentration carry out essential signaling and messenger functions (see Mitohormesis ). However, by definition, antioxidants cannot differentiate between the two functions of ROS and interfere with both potentially harmful and protective effects. Sufficient studies are not yet available as to whether the antioxidants contained in fresh foods such as fruit and vegetables have a therapeutic effect. The association of increased fruit and vegetable consumption with increased life expectancy or reduced cancer risk, which has been observed in many ways, is no proof of the effectiveness of antioxidants: fiber in fruits and vegetables, for example, can also be responsible for this association.

See also

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  1. ↑ a b c d e f R. F. Schmidt among others: Physiology of humans. Springer, 2007, ISBN 978-3-540-32908-4 , pp. 957 ff. (Online)
  2. ^ CV of Helmut Sies
  3. ↑ David Heber, George L. Blackburn, Vay Liang W. Go, John Milner (Eds.): Nutritional Oncology. Academic Press, 2006, ISBN 0-12-088393-7 , p. 314.
  4. ↑ Schulz, TJ. et al. (2007): Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. In: Cell Metabolism . 6 (4); 280-293; PMID 17908557
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  8. ^ Moustafa AA El-Taieb, Ralf Herwig, Essam A. Nada, Joachim Greilberger, Michael Marberger: Oxidative stress and epididymal sperm transport, motility and morphological defects . In: European Journal of Obstetrics & Gynecology and Reproductive Biology . tape 144 , Supplement 1. ELSEVIER, 2009, p. S199 – S203 , doi : 10.1016 / j.ejogrb.2009.02.018 ( elsevier.com [accessed on September 27, 2019]).
  9. ↑ Ralf Herwig, Christian Knoll, Melanie Planyavsky, Ali Pourbiabany, Joachim Greilberger: Proteomic analysis of seminal plasma from infertile patients with oligoasthenoteratozoospermia due to oxidative stress and comparison with fertile volunteers . In: Fertility and Sterility . tape 100 , no. 2 , 2013, p. 355–366.e2 , doi : 10.1016 / j.fertnstert.2013.03.048 ( elsevier.com [accessed September 27, 2019]).
  10. ↑ Bjelakovic, G. et al. (2007): Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis . In: JAMA 299 (7); 842-857; PMID 17327526
  11. ↑ Bjelakovic, G. et al. (2012): Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases . In: Cochrane Database Syst Rev 14; CD007176; PMID 22419320
  12. ↑ C. Kleinschnitz et al: Post-stroke inhibition of induced NADPH oxidase type 4 prevents oxidative stress and neurodegeneration. In: PLoS Biol. 8, (2010).
  13. ↑ Ch. Sohr: Oxidative stress in diabetic neuropathy. Medical Faculty »Institutes» German Diabetes Center DDZ, 2007. (online)
  14. ^ KA Jellinger: Recent developments in the pathology of Parkinson's disease. In: Journal of Neural Transmission . Vol. 62 (2002), pp. 347-376.
  15. ^ E. Kienzl et al .: Iron as a catalyst for oxidative stress in the pathogenesis of Parkinson's disease? In: Life Science. Volume 65 (1999), pp. 1973-1976.
  16. ↑ H. Heinle: Oxidative stress and vascular function: Studies on the influence of hydroperoxides on contraction and endothelial function in arteries. Dissertation, Faculty of Chemistry and Pharmacy, University of Tübingen, 2004.
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