Oxidative stress reflects an imbalance between the systemic manifestation of
reactive oxygen species and a biological system's ability to readily
detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal
redox
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or ...
state of cells can cause toxic effects through the production of
peroxide
In chemistry, peroxides are a group of compounds with the structure , where R = any element. The group in a peroxide is called the peroxide group or peroxo group. The nomenclature is somewhat variable.
The most common peroxide is hydrogen p ...
s and
free radicals that damage all components of the cell, including
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s,
lipid
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids in ...
s, and
DNA. Oxidative stress from
oxidative metabolism causes base damage, as well as
strand breaks in DNA. Base damage is mostly indirect and caused by the reactive oxygen species generated, e.g., O
2− (
superoxide radical), OH (
hydroxyl
In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydrox ...
radical) and H
2O
2 (
hydrogen peroxide
Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3 ...
). Further, some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause disruptions in normal mechanisms of
cellular signaling.
In humans, oxidative stress is thought to be involved in the development of
attention deficit hyperactivity disorder
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...
,
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
,
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...
,
Lafora disease
Lafora disease is a rare, adult-onset and autosomal recessive genetic disorder which results in myoclonus epilepsy and usually results in death several years after the onset of symptoms. The disease is characterized by the accumulation of inclusi ...
,
Alzheimer's disease,
atherosclerosis,
heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...
,
myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which ma ...
,
fragile X syndrome,
sickle-cell disease
Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red ...
,
lichen planus,
vitiligo,
autism,
infection
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...
,
chronic fatigue syndrome,
and
depression;
however, reactive oxygen species can be beneficial, as they are used by the
immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
as a way to attack and kill
pathogen
In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a g ...
s.
Short-term oxidative stress may also be important in prevention of
aging
Ageing ( BE) or aging ( AE) is the process of becoming older. The term refers mainly to humans, many other animals, and fungi, whereas for example, bacteria, perennial plants and some simple animals are potentially biologically immortal. In ...
by induction of a process named
mitohormesis
Hormesis is a characteristic of many biological processes, namely a biphasic or triphasic response to exposure to increasing amounts of a substance or condition. Within the hormetic zone, the biological response to low exposures to toxins and othe ...
,
and is required to initiate stress response processes in plants.
Chemical and biological effects
Chemically, oxidative stress is associated with increased production of oxidizing species or a significant decrease in the effectiveness of
antioxidant
Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubrica ...
defenses, such as
glutathione.
The effects of oxidative stress depend upon the size of these changes, with a cell being able to overcome small perturbations and regain its original state. However, more severe oxidative stress can cause cell death, and even moderate oxidation can trigger
apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes in ...
, while more intense stresses may cause
necrosis.
Production of reactive oxygen species is a particularly destructive aspect of oxidative stress. Such species include
free radicals and
peroxide
In chemistry, peroxides are a group of compounds with the structure , where R = any element. The group in a peroxide is called the peroxide group or peroxo group. The nomenclature is somewhat variable.
The most common peroxide is hydrogen p ...
s. Some of the less reactive of these species (such as
superoxide) can be converted by
oxidoreduction reactions with
transition metal
In chemistry, a transition metal (or transition element) is a chemical element in the d-block of the periodic table (groups 3 to 12), though the elements of group 12 (and less often group 3) are sometimes excluded. They are the elements that can ...
s or other redox cycling compounds (including
quinones) into more aggressive radical species that can cause extensive cellular damage.
Most long-term effects are caused by damage to DNA.
DNA damage induced by
ionizing radiation is similar to oxidative stress, and these lesions have been implicated in
aging
Ageing ( BE) or aging ( AE) is the process of becoming older. The term refers mainly to humans, many other animals, and fungi, whereas for example, bacteria, perennial plants and some simple animals are potentially biologically immortal. In ...
and cancer. Biological effects of single-base damage by radiation or oxidation, such as
8-oxoguanine and
thymine glycol
Thymine glycol (5,6-dihydroxy-5,6-dihydrothymine) is one of the principal DNA lesions that can be induced by oxidation and ionizing radiation. Aging, stroke
The rate at which oxidative reactions generate thymine glycol and thymidine glycol in th ...
, have been extensively studied. Recently the focus has shifted to some of the more complex lesions. Tandem DNA lesions are formed at substantial frequency by ionizing radiation and metal-
catalyzed H
2O
2 reactions. Under
anoxic conditions, the predominant double-base lesion is a species in which C8 of guanine is linked to the 5-methyl group of an adjacent 3'-thymine (G
,5- Me).
Most of these
oxygen
Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements ...
-derived species are produced by normal
aerobic metabolism. Normal cellular defense mechanisms destroy most of these. Repair of oxidative damages to DNA is frequent and ongoing, largely keeping up with newly induced damages. In rat urine, about 74,000 oxidative DNA adducts per cell are excreted daily.
There is also a steady state level of oxidative damages in the DNA of a cell. There are about 24,000 oxidative DNA adducts per cell in young rats and 66,000 adducts per cell in old rats.
Likewise, any damage to cells is constantly repaired. However, under the severe levels of oxidative stress that cause necrosis, the damage causes
ATP depletion, preventing controlled apoptotic death and causing the cell to simply fall apart.
Polyunsaturated fatty acids
Polyunsaturated fatty acids (PUFAs) are fatty acids that contain more than one double bond in their backbone. This class includes many important compounds, such as essential fatty acids and those that give drying oils their characteristic pr ...
, particularly
arachidonic acid and
linoleic acid
Linoleic acid (LA) is an organic compound with the formula COOH(CH2)7CH=CHCH2CH=CH(CH2)4CH3. Both alkene groups are ''cis''. It is a fatty acid sometimes denoted 18:2 (n-6) or 18:2 ''cis''-9,12. A linoleate is a salt or ester of this acid.
...
, are primary targets for free radical and singlet oxygen oxidations. For example, in tissues and cells, the free radical oxidation of linoleic acid produces
racemic mixtures of 13-hydroxy-9''Z'',11''E''-octadecadienoic acid, 13-hydroxy-9''E'',11''E''-octadecadienoic acid, 9-hydroxy-10''E'',12-''E''-octadecadienoic acid (9-EE-HODE), and 11-hydroxy-9''Z'',12-''Z''-octadecadienoic acid as well as
4-Hydroxynonenal while singlet oxygen attacks linoleic acid to produce (presumed but not yet proven to be racemic mixtures of) 13-hydroxy-9''Z'',11''E''-octadecadienoic acid, 9-hydroxy-10''E'',12-''Z''-octadecadienoic acid, 10-hydroxy-8''E'',12''Z''-octadecadienoic acid, and 12-hydroxy-9''Z''-13-''E''-octadecadienoic (see
13-Hydroxyoctadecadienoic acid and
9-Hydroxyoctadecadienoic acid).
Similar attacks on arachidonic acid produce a far larger set of products including various
isoprostanes The isoprostanes are prostaglandin-like compounds formed ''in vivo'' from the free radical-catalyzed peroxidation
of essential fatty acids (primarily arachidonic acid) without the direct action of cyclooxygenase (COX) enzymes. The compounds were ...
, hydroperoxy- and hydroxy- eicosatetraenoates, and 4-hydroxyalkenals.
While many of these products are used as markers of oxidative stress, the products derived from linoleic acid appear far more predominant than arachidonic acid products and therefore easier to identify and quantify in, for example, atheromatous plaques.
Certain linoleic acid products have also been proposed to be markers for specific types of oxidative stress. For example, the presence of racemic 9-HODE and 9-EE-HODE mixtures reflects free radical oxidation of linoleic acid whereas the presence of racemic 10-hydroxy-8''E'',12''Z''-octadecadienoic acid and 12-hydroxy-9''Z''-13-''E''-octadecadienoic acid reflects singlet oxygen attack on linoleic acid.
In addition to serving as markers, the linoleic and arachidonic acid products can contribute to tissue and/or DNA damage but also act as signals to stimulate pathways which function to combat oxidative stress.
Table adapted from.
Production and consumption of oxidants
One source of reactive oxygen under normal conditions in humans is the leakage of activated oxygen from
mitochondria during
oxidative phosphorylation. ''
E. coli'' mutants that lack an active electron transport chain produce as much
hydrogen peroxide
Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3 ...
as wild-type cells, indicating that other enzymes contribute the bulk of oxidants in these organisms. One possibility is that multiple redox-active
flavoproteins all contribute a small portion to the overall production of oxidants under normal conditions.
Other enzymes capable of producing superoxide are
xanthine oxidase, NADPH oxidases and
cytochromes P450. Hydrogen peroxide is produced by a wide variety of enzymes including several oxidases. Reactive oxygen species play important roles in cell signalling, a process termed
redox signaling. Thus, to maintain proper cellular
homeostasis
In biology, homeostasis ( British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and ...
, a balance must be struck between reactive oxygen production and consumption.
The best studied cellular antioxidants are the enzymes
superoxide dismutase
Superoxide dismutase (SOD, ) is an enzyme that alternately catalyzes the dismutation (or partitioning) of the superoxide () radical into ordinary molecular oxygen (O2) and hydrogen peroxide (). Superoxide is produced as a by-product of oxygen ...
(SOD),
catalase, and
glutathione peroxidase. Less well studied (but probably just as important) enzymatic antioxidants are the peroxiredoxins and the recently discovered
sulfiredoxin. Other enzymes that have antioxidant properties (though this is not their primary role) include paraoxonase, glutathione-S transferases, and aldehyde dehydrogenases.
The amino acid methionine is prone to oxidation, but oxidized methionine can be reversible. Oxidation of methionine is shown to inhibit the phosphorylation of adjacent Ser/Thr/Tyr sites in proteins.
This gives a plausible mechanism for cells to couple oxidative stress signals with cellular mainstream signaling such as phosphorylation.
Diseases
Oxidative stress is suspected to be important in
neurodegenerative disease
A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophi ...
s including
Lou Gehrig's disease
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most com ...
(aka MND or ALS),
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...
,
Alzheimer's disease,
Huntington's disease
Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an uns ...
,
depression, and
multiple sclerosis.
It is also indicated in Neurodevelopmental conditions such as
Autism Spectrum Disorder.
Indirect evidence via monitoring biomarkers such as reactive oxygen species, and
reactive nitrogen species production indicates oxidative damage may be involved in the pathogenesis of these diseases,
while cumulative oxidative stress with disrupted mitochondrial respiration and mitochondrial damage are related to Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases.
Oxidative stress is thought to be linked to certain
cardiovascular disease, since oxidation of
LDL in the vascular
endothelium
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the ve ...
is a precursor to
plaque formation. Oxidative stress also plays a role in the
ischemic cascade due to oxygen
reperfusion injury following
hypoxia. This cascade includes both
strokes and
heart attacks
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...
. Oxidative stress has also been implicated in
chronic fatigue syndrome (ME/CFS). Oxidative stress also contributes to tissue injury following irradiation and
hyperoxia, as well as in diabetes. In hematological cancers, such as leukemia, the impact of oxidative stress can be bilateral. Reactive oxygen species can disrupt the function of immune cells, promoting
immune evasion of leukemic cells. On the other hand, high levels of oxidative stress can also be selectively toxic to cancer cells.
Oxidative stress is likely to be involved in age-related development of cancer. The reactive species produced in oxidative stress can cause direct damage to the DNA and are therefore
mutagenic, and it may also suppress
apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes in ...
and promote proliferation, invasiveness and
metastasis
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, the ...
.
Infection by ''
Helicobacter pylori'' which increases the production of reactive oxygen and nitrogen species in human stomach is also thought to be important in the development of
gastric cancer
Stomach cancer, also known as gastric cancer, is a cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes, including gastric adenocarcinomas. Lym ...
.
Antioxidants as supplements
The use of antioxidants to prevent some diseases is controversial.
In a high-risk group like smokers, high doses of
beta carotene increased the rate of lung cancer since high doses of beta-carotene in conjunction of high
oxygen tension due to smoking results in a
pro-oxidant Pro-oxidants are chemicals that induce oxidative stress, either by generating reactive oxygen species or by inhibiting antioxidant systems. The oxidative stress produced by these chemicals can damage cells and tissues, for example an overdose of th ...
effect and an antioxidant effect when oxygen tension is not high.
In less high-risk groups, the use of
vitamin E appears to reduce the risk of
heart disease.
However, while consumption of food rich in vitamin E may reduce the risk of coronary heart disease in middle-aged to older men and women, using vitamin E supplements also appear to result in an increase in total mortality, heart failure, and
hemorrhagic stroke. The American Heart Association therefore recommends the consumption of food rich in antioxidant vitamins and other nutrients, but does not recommend the use of vitamin E supplements to prevent cardiovascular disease.
In other diseases, such as
Alzheimer's
Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As t ...
, the evidence on vitamin E supplementation is also mixed.
Since dietary sources contain a wider range of carotenoids and vitamin E tocopherols and tocotrienols from whole foods, ''ex post facto'' epidemiological studies can have differing conclusions than artificial experiments using isolated compounds.
AstraZeneca's radical scavenging
nitrone drug
NXY-059
Disufenton sodium (Cerovive, OKN-007, NXY-059, HPN-07) is a free radical trapping nitrone-based antioxidant compound that has been under development for several medical conditions.
Chemistry
Disufenton sodium is the disulfonyl derivative of the ...
shows some efficacy in the treatment of stroke.
Oxidative stress (as formulated in
Denham Harman's
free-radical theory of aging
The free radical theory of aging (FRTA) states that organisms age because cells accumulate free radical damage over time. A free radical is any atom or molecule that has a single unpaired electron in an outer shell.Erbas M, Sekerci H. "Importance ...
) is also thought to contribute to the aging process. While there is good evidence to support this idea in model organisms such as ''
Drosophila melanogaster
''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...
'' and ''
Caenorhabditis elegans'',
recent evidence from
Michael Ristow
Michael Ristow (b April 24, 1967) is a German medical researcher who has published influential articles on biochemical aspects of mitochondrial metabolism and particularly the possibly health-promoting role of reactive oxygen species in diseases ...
's laboratory suggests that oxidative stress may also promote life expectancy of ''Caenorhabditis elegans'' by inducing a secondary response to initially increased levels of reactive oxygen species.
The situation in mammals is even less clear.
Recent
epidemiological
Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and determinants of health and disease conditions in a defined population.
It is a cornerstone of public health, and shapes policy decisions and evid ...
findings support the process of
mitohormesis
Hormesis is a characteristic of many biological processes, namely a biphasic or triphasic response to exposure to increasing amounts of a substance or condition. Within the hormetic zone, the biological response to low exposures to toxins and othe ...
, however a 2007 meta-analysis indicating studies with a low risk of bias (randomization, blinding, follow-up) find that some popular antioxidant supplements (Vitamin A, Beta Carotene, and Vitamin E) may increase mortality risk (although studies more prone to bias reported the reverse).
[. See also th]
letter
to JAMA by Philip Taylor and Sanford Dawsey Sanford may refer to:
People
*Sanford (given name), including a list of people with the name
*Sanford (surname), including a list of people with the name
Places United States
* Sanford, Alabama, a town in Covington County
* Sanford, Colorado ...
and th
reply
by the authors of the original paper.
The USDA removed the table showing the
Oxygen Radical Absorbance Capacity
Oxygen radical absorbance capacity (ORAC) was a method of measuring antioxidant capacities in biological samples ''in vitro''. Because no physiological proof '' in vivo'' existed in support of the free-radical theory or that ORAC provided informat ...
(ORAC) of Selected Foods Release 2 (2010) table due to the lack of evidence that the antioxidant level present in a food translated into a related antioxidant effect in the body.
Metal catalysts
Metals such as
iron
Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in ...
,
copper
Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pink ...
,
chromium,
vanadium, and
cobalt
Cobalt is a chemical element with the symbol Co and atomic number 27. As with nickel, cobalt is found in the Earth's crust only in a chemically combined form, save for small deposits found in alloys of natural meteoric iron. The free element, p ...
are capable of redox cycling in which a single
electron
The electron ( or ) is a subatomic particle with a negative one elementary electric charge. Electrons belong to the first generation of the lepton particle family,
and are generally thought to be elementary particles because they have n ...
may be accepted or donated by the metal. This action catalyzes production of reactive
radicals and reactive oxygen species. The presence of such metals in biological systems in an uncomplexed form (not in a protein or other protective metal complex) can significantly increase the level of oxidative stress. These metals are thought to induce
Fenton reactions and the Haber-Weiss reaction, in which
hydroxyl radical is generated from hydrogen peroxide. The hydroxyl radical then can modify amino acids. For example, meta-
tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the G ...
and ortho-
tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the G ...
form by hydroxylation of
phenylalanine. Other reactions include lipid peroxidation and oxidation of nucleobases. Metal-catalyzed oxidations also lead to irreversible modification of arginine, lysine, proline, and threonine. Excessive oxidative-damage leads to protein degradation or aggregation.
The reaction of transition metals with proteins oxidated by reactive oxygen or nitrogen species can yield reactive products that accumulate and contribute to aging and disease. For example, in
Alzheimer's
Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As t ...
patients, peroxidized lipids and proteins accumulate in lysosomes of the brain cells.
Non-metal redox catalysts
Certain organic compounds in addition to metal redox catalysts can also produce reactive oxygen species. One of the most important classes of these is the
quinones. Quinones can redox cycle with their conjugate
semiquinone
Semiquinone (or ubisemiquinone) is a free radical resulting from the removal of one hydrogen atom with its electron during the process of dehydrogenation of a hydroquinone, such as hydroquinone itself or catechol, to a quinone or alternatively the ...
s and
hydroquinone
Hydroquinone, also known as benzene-1,4-diol or quinol, is an aromatic organic compound that is a type of phenol, a derivative of benzene, having the chemical formula C6H4(OH)2. It has two hydroxyl groups bonded to a benzene ring in a ''pa ...
s, in some cases catalyzing the production of superoxide from dioxygen or hydrogen peroxide from superoxide.
Immune defense
The immune system uses the lethal effects of oxidants by making the production of oxidizing species a central part of its mechanism of killing pathogens; with activated
phagocytes producing both reactive oxygen and nitrogen species. These include superoxide , nitric oxide (•NO) and their particularly reactive product, peroxynitrite (ONOO-).
Although the use of these highly reactive compounds in the cytotoxic response of phagocytes causes damage to host tissues, the non-specificity of these oxidants is an advantage since they will damage almost every part of their target cell.
This prevents a pathogen from escaping this part of immune response by mutation of a single molecular target.
Male infertility
Sperm DNA fragmentation
DNA fragmentation is the separation or breaking of DNA strands into pieces. It can be done intentionally by laboratory personnel or by cells, or can occur spontaneously. Spontaneous or accidental DNA fragmentation is fragmentation that gradually a ...
appears to be an important factor in the
aetiology of
male infertility, since men with high DNA fragmentation levels have significantly lower odds of conceiving.
Oxidative stress is the major cause of DNA fragmentation in
spermatozoa
A spermatozoon (; also spelled spermatozoön; ; ) is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote. (A zygote is a single cell, with a complete set of chromos ...
.
A high level of the oxidative DNA damage
8-oxo-2'-deoxyguanosine is associated with abnormal spermatozoa and male infertility.
Aging
In a rat model of premature aging, oxidative stress induced
DNA damage
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA d ...
in the
neocortex and
hippocampus
The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic syste ...
was substantially higher than in normally aging control rats.
Numerous studies have shown that the level of 8-oxo-2'-deoxyguanosine, a product of oxidative stress, increases with age in the brain and muscle DNA of the
mouse,
rat,
gerbil and
human
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, cultu ...
. Further information on the association of oxidative DNA damage with aging is presented in the article
DNA damage theory of aging. However, it was recently shown that the fluoroquinolone antibiotic
Enoxacin
EnoxacinEnoxacin is sold under the following trade names: Almitil, Bactidan, Bactidron, Comprecin, Enoksetin, Enoxen, Enroxil, Enoxin, Enoxor, Flumark, Penetrex, Gyramid, Vinone. is an oral broad-spectrum fluoroquinolone antibacterial agent used in ...
can diminish aging signals and promote lifespan extension in nematodes ''C. elegans ''by inducing oxidative stress.
Origin of eukaryotes
The
great oxygenation event began with the biologically induced appearance of oxygen in the
Earth's atmosphere
The atmosphere of Earth is the layer of gases, known collectively as air, retained by Earth's gravity that surrounds the planet and forms its planetary atmosphere. The atmosphere of Earth protects life on Earth by creating pressure allowing fo ...
about 2.45 billion years ago. The rise of oxygen levels due to
cyanobacteria
Cyanobacteria (), also known as Cyanophyta, are a phylum of gram-negative bacteria that obtain energy via photosynthesis. The name ''cyanobacteria'' refers to their color (), which similarly forms the basis of cyanobacteria's common name, bl ...
l
photosynthesis
Photosynthesis is a process used by plants and other organisms to convert light energy into chemical energy that, through cellular respiration, can later be released to fuel the organism's activities. Some of this chemical energy is stored in ...
in ancient microenvironments was probably highly toxic to the surrounding biota. Under these conditions, the selective pressure of oxidative stress is thought to have driven the evolutionary transformation of an
archaeal lineage into the first
eukaryotes.
Oxidative stress might have acted in synergy with other environmental stresses (such as
ultraviolet
Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30 PHz) to 400 nm (750 THz), shorter than that of visible light, but longer than X-rays. UV radiation ...
radiation and/or
desiccation) to drive this selection. Selective pressure for efficient repair of oxidative DNA damages may have promoted the evolution of eukaryotic sex involving such features as cell-
cell fusion Cell fusion is an important cellular process in which several uninucleate cells (cells with a single nucleus) combine to form a multinucleate cell, known as a syncytium. Cell fusion occurs during differentiation of myoblasts, osteoclasts and tropho ...
s,
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is co ...
-mediated
chromosome
A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins ar ...
movements and emergence of the
nuclear membrane.
Thus, the evolution of
meiotic
Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately res ...
sex and eukaryogenesis may have been inseparable processes that evolved in large part to facilitate repair of oxidative DNA damages.
COVID-19 and cardiovascular injury
It has been proposed that oxidative stress may play a major role to determine cardiac complications in COVID-19.
See also
*
Antioxidative stress
Antioxidative stress is an overabundance of bioavailable antioxidant compounds that interfere with the immune system's ability to neutralize pathogenic threats. The fundamental opposite is oxidative stress, which can lead to such disease states as ...
*
Acatalasia
Acatalasia is an autosomal recessive peroxisomal disorder caused by absent or very low levels of the enzyme catalase. Catalase breaks down hydrogen peroxide in cells into water and oxygen. Low levels of catalase can cause hydrogen peroxide to bui ...
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Bruce Ames
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Malondialdehyde, an oxidative stress marker
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Mitochondrial free radical theory of aging
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Mitohormesis
Hormesis is a characteristic of many biological processes, namely a biphasic or triphasic response to exposure to increasing amounts of a substance or condition. Within the hormetic zone, the biological response to low exposures to toxins and othe ...
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Nitric oxide
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Pro-oxidant Pro-oxidants are chemicals that induce oxidative stress, either by generating reactive oxygen species or by inhibiting antioxidant systems. The oxidative stress produced by these chemicals can damage cells and tissues, for example an overdose of th ...
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Reductive stress Reductive stress (RS) is defined as an abnormal accumulation of reducing equivalents despite being in the presence of intact oxidation and reduction systems. A redox reaction involves the transfer of electrons from reducing agents (reductants) to ox ...
References
{{Authority control
Cell biology
Chemical pathology
Alzheimer's disease
Senescence