can act as oxidant (e. g. ferric ion) or reductant (e. g. ferrous ion) depending on its chemical structure
and/or its physical/chemical “environment” in this paper we will refer to such common “absolute”
definition of redox reactions (3).
The most biologically relevant oxidising species involved in stress response are (free) radicals (e. g.
hydroxyl radical, HO.) which have been defined as single or grouped atoms where there is one atom
showing in an external orbital one instead of two electrons (3). This latter feature makes “reactive” the
oxidising specie that in order to reach its stability (all coupled electrons) tends to extract the lacking
electron from the reducing specie (3). Such “reactivity” is inversely related to the half-life of free
radicals and although some free radicals like hydroxyl radical are very reactive and show a very short
life other free radicals like triphenyl-methyl are stable and long-living (3). Noticeably oxidising species
include also non-radical species like hydrogen peroxide (H2O2) which molecule, for instance, although
contains all paired electrons, is able to extract one electron from chloride thus oxidising it to
hypochlorite through the enzyme myeloperoxidase (3). Moreover even if oxidising species are referred
mostly to oxygen as electron-lacking atom they can be “centred” also on other elements, like nitrogen,
carbon, sulphur or chlorine. Therefore in this paper we will use the commonest terms “reactive oxygen
species” as synonymous of “reactive oxidising species” (ROS) to indicate any
oxygen/nitrogen/carbon/sulphur/chlorine radical/non-radical reactive oxidising specie e. g. hydroxyl
radical, nitric oxide, alkoxyl radical, thiyl radical, and hypochlorite, respectively (3).
In living organisms ROS are physiologically as well as continuously generated during the normal
metabolism by means of two mechanisms: the first one is mediated by enzymes while the second one is
triggered by physical agents or transition metals (3, 4). The enzyme-mediated production of ROS is
due to the activation of catalytic proteins that are located on the plasmamembrane, into the
mitochondria, in the endoplasmic reticulum (microsomes), into the peroxisomes and in the cytosol (3,
4); interestingly the biosynthesis as well as the catabolism of adrenaline, a mediator of emotional
stress, involves the production of ROS (5). Among the non-enzymatic mediated ROS reactions, there is
the homolytic breakdown where the administration of energy (as ionising radiation or heat) breaks a
covalent bond of the target molecule thus generating two distinct radical species both showing one
unpaired electron; a biologically relevant example of homolytic reaction is the water breakdown due to
X-ray (radiolysis) or UV-ray (photolysis) that generates two radicals, i. e. the hydrogen atom and the
hydroxyl specie. Another non-enzymatic mechanism involved in ROS generation is the production of
alkoxyl radical (RO.) and hydroperoxyl radical (ROO.) from peroxides (ROOH) that is mediated by a transition metal in ionic form, e. g. iron (Fe2+/Fe3+) or copper (Cu+/Cu2+), according to the so-called

Fenton’s reaction (3, 4, 6).
The main action of ROS is the extraction of one electron from another chemical specie. Such target specie can be any organic compound but generally speaking the preferential targets of oxidative processes are all the molecules showing at least a double covalent bond (e. g. –C=C–) because the second
bond (p) is a relatively free couple of electrons (3, 4). On this basis a descendent scale of susceptibility to
oxidation has been proposed for the most common biomolecules: unsatured fatty acids, amino
acids/proteins, nucleic acids and carbohydrates. Selective targets of ROS are also reduced thiol groups
(-SH) (e. g. from cysteine) that can be reversibly or irreversibly oxidized (7).
In any case by extracting one electron ROS can change not only the structure but also the function of
the target biomolecule with final biological effects that can result positive, negative or apparently
neutral, depending on the environmental conditions. By a physiological point of view such reactions
being highly conserved during the evolution seems to have been planned to allow the adaptation of living
organisms either to external or internal stressors (8).
In other words exogenous and/or endogenous stimuli may trigger the production of ROS that
activate/inhibit specific biochemical pathways inside the cells thus allowing them to face environmental
changes. For instance plants can adapt to many changing weather conditions (light to dark, dryness to
humidity) thanks to the production of hydrogen peroxide and other ROS (9, 10). Similarly animals seems
to exploit analogous mechanisms of adaptation by means of mild, transient and reversible protein
thiols-mediated oxidative changes which main goal is to modulate key signalling/transduction molecular
pathways of inflammatory/immune/toxic responses that are responsible of cell homeostasis and survival
(7, 11). A paradigmatic example of such mechanism is provided by the system ASK1-TRx, although redox
changes of thiol groups are only a piece of this intricate biochemical puzzle (12). A specific example of
ROS-mediated mechanism of adaptation is provided by the production of oxidants (e. g. hydrogen
peroxide and hypochlorous acid) by inflammatory cells in order to protect the tissues against bacterial
infections (13). Another relevant example of physiological modulation by ROS is provided by nitric oxide
pathway (10, 14).
The generally low energy expenditure required, the fast and easy way of production, the high
diffusibility, together with the very short half-life make ROS-mediated reactions really essential for
survival especially in a context of an autacoid modulation. Of course the success of such mechanisms is
closely related to the efficacy of their restoring machinery. As with the neurotransmission mechanisms,
where the mediator (e. g. acetylcholine) after acting must be destroyed or inactivated (e. g. by
acethylcholinesterase), even ROS must be neutralized, after having successfully reached their target
molecules (9, 10, 14). For this reason, in the course of millions of years of evolution, the living organisms
have developed the so-called “antioxidants” – i. e. exogenous or endogenous compounds/enzymes like
ascorbic acid, tocopherols, polyphenols, superoxide dismutase, catalase, glutathione peroxidase, and so
on – that act as “physiological modulators” of ROS (15, 16). Indeed the main role of the antioxidant
system is not to fight ROS but rather “to modulate” their actions and to avoid their unwanted side effects
(see below) (2, 11, 17). In such interplay the production of antioxidants can be also directly stimulated by
ROS themselves, as proved for Nrf-2 system that provides an excellent example of signal transduction
involving the DNA (18).
Nowadays these herein shown processes can be included in the modern concept of “oxidative eu-stress”
(EU-OS) that means “good or favourable stress”. Indeed EU-OS is by itself a “positive” adaptive
mechanism because it allows the living organism – through an appropriate oxidation – to successfully
respond to an environmental change (stimulus or stressor) (8). Much more EU-OS should be considered
as a necessary mechanism of homeostasis like the “emotional stress” (1). Indeed EU-OS and emotional
stress share many common features and in some way the first one provides a solid biochemical basis for

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the second one (2, 6, 17). Furthermore it seems that the evolution of living organisms – together with
their metabolic, energetic and reproductive changes – during the last billion of years, was driven just by
redox changes (which witnesses are both the increased levels of oxygen in the atmosphere and cysteine
in the proteome) according to a “redox code” which expression is modulated by the intracellular[NAD+/NADH+H+] and [(-SH)2/(-S-S-)] ratios (8).
Going back to the basic concept of EU-OS, the physiological modulation by the commonly called
“antioxidants” is crucial because a ROS as opposed to a neurotransmitter (or a hormone), especially if
in excess, because acts in a non-specific way, can extract its lacking electron not only from its specific
targets but also from other bio-molecules like unsatured fatty acids or nucleic acid, that can result
permanently and irreversibly oxidised (15). In turn these events can lead to intracellular and/or
extracellular injuries that are finally responsible of functional and/or organic damages potentially in
all cells, tissues and organs, with a loss of whole body wellness (3).
To define these phenomena from the pathophysiological view point the term “oxidative di-stress” or
“oxidative stress” (OS) as such has been coined (3, 4, 19). Oxidative stress is more than a “break of the
balance between ROS and antioxidants” as often improperly described in almost all academic papers
(3). Rather, OS highlights the inability of the host’s redox system to manage the oxidative chain
reactions triggered by the stressor/stimulus because ROS are in excess and/or the “antioxidant” system
of modulation is ineffective (20). A classical example of oxidative di-stress is provided by the
inappropriate leukocytes ROS production in the periodontitis, where the uncontrolled production of
ROS can lead to the destruction not only of the stressors, i. e. the bacteria, but also of the organs
involved, i. e. the teeth (21).
Oxidative stress is generally recognized to play a variable pathogenic role in early aging and in
several inflammatory and/or metabolic and/or degenerative diseases including arthritis, diabetes,
atherosclerosis and arterial hypertension (and their consequences, such as stroke and myocardial
infarction), Alzheimer’s disease, Parkinson’s disease, cancer, and so on (22).
However OS is not a “disease” in the traditional sense of the word. It is the unwanted effect of redox
system dysfunction that can impact, often deceitfully, the onset and/or the course of several basic
diseases. As it is not a classical disease, OS does not show a specific clinical picture but hides itself
behind the symptoms and signs of the basic underlying sickness (e. g. arterial hypertension). Therefore,
OS should be considered as an emerging health risk factor that can be identified only through specific
laboratory tests (22, 23).
In this object the above generally accepted definition of OS provides a suitable rationale to measure
redox homeostasis in Humans. Indeed an increased production of ROS and/or a decreased efficacy of
the antioxidant defence system inside or outside the cells may lead to the (per)oxidation of a number of
biomolecules and/or to the drop of antioxidants level/activity either in tissues or extracellular fluids
which may represent the optimal specimens where to evaluate the OS (24). Therefore any evaluation of
OS must be global i. e. must take in account not only the oxidant but also the antioxidant processes.
In order to identify subjects who are at risk for OS (because they are exposed to potential sources of
ROS or they are affected by OS-related diseases or they are under treatment for OS-related therapies
like radiotherapy) the first line approach to measure OS in clinical practice is to evaluate both the
so-called total oxidant capacity/activity e. g. by means of d-ROMs test and the so-called total
antioxidant capacity/activity e. g. by means of BAP test, anti-ROMs test, and OXY-adsorbent test on
blood plasma/serum samples (24, 25). Indeed almost all these tests showed appropriate and easy to
perform and displayed favourable benefits/costs ratios, also due to the possibility to be performed
through a photometer that is the most common chemical analytical device (24, 25). For instance
d-ROMs and BAP test can be performed “at-a-glance” by the doctor his-self in any clinical settings
including ambulatories through dedicated and integrated devices e. g. CARPE DIEM or CARRIO DUO

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systems (Wismerll Ltd, Tokyo, Japan), that incorporate a small centrifuge, a dry thermostated block and
a photometric reading cell; this approach allows the clinician to do the results to the patient in a few
minutes (26, 27). Of course when the main purpose of such tests is the screening and/or the monitoring of
OS in wider samples of population these analyses can be performed through multiple analysers (28).
When the main aim of OS measurement is a particular clinic need (e. g. to monitor the effect of the
vitamin E supplementation on lipid peroxidation in a patient suffering from cardiovascular diseases) or
a clinical research (e. g. to evaluate in a controlled clinical trial on hypertensive subjects the impact of a
calcium blocker drug on redox homeostasis) a second line of more specific tests for oxidative and
antioxidant processes, respectively, is available.
The golden standard approach to evaluate oxidative processes is to measure directly the level of
oxidant species in the biological specimen (e. g. blood, urine, seminal fluid and so on) (22, 24, 25). This
goal can be achieved by using electron spin resonance for radical ROS (like hydroxyl or peroxyl radicals),
or other photometric/fluorescent methods for non-radical ROS (like hydrogen peroxide). When such
direct measurement of ROS is not possible, different methods, referred to as fingerprinting, must be
applied (24, 25). According to this approach, a radical is inferred from the molecular nature of the
damage it causes to biological molecules. Indeed once the OS level is great enough to overcome the
antioxidant defences, ROS can theoretically damage every component of the cell, including lipids, amino
acids, proteins, and nucleic acids, thus generating oxidized by-products; these damaged molecules – or
the products resulting from their breakdown – can be considered as a “fingerprinting” (22, 24, 25).
Therefore oxidative damage is presumed to happen in vivo when it generates identifiable and
quantifiable specific by-products in vitro, like hydroperoxides, chloramines, advanced glycosylation end
products, isoprostanes, 8-OH-dG) (22, 24, 25), that are assumed to be biomarkers of oxidative status.
Notably, some of these “biomarkers”, like hydroperoxides, can also act as “amplifiers” of oxidative
damage, which underscores the importance of detecting these molecules in order to reduce not only the
effect but also the cause of OS (22, 24, 25).
On the opposite side, in order to evaluate the antioxidant defences many direct methods allow measure
the level of water/lipid-soluble antioxidants (e. g. vitamin C and E) as well as the activity of enzymes
that are involved in redox reactions (e. g. superoxide dismutase, catalases, and peroxidases) in tissues or
biological fluids (22, 24, 25).
In this scenario, the systematic evaluation in biological samples (tissues or fluids) of primary oxidant
chemical species and their derivatives, like hydroperoxides, as well as the dosing of antioxidant
compounds/activities, like selenium and glutathione peroxidase, respectively, are not a terminal “ring”
in the diagnostic chain on informational flow in biological systems (DNA→PROTEINS→
METABOLITES) but can take a “central”place compared to genomics, transcriptomics, proteomics and
metabolomics (24, 29). For this reason very recently we introduced the novel concept of “redoxomics” (a
term previously and ambiguously used to identify only some oxidised by-products in the field of
proteomics) (29, 30).
Redoxomics is a novel branch of “applied biochemistry” and “molecular diagnostics” having the
following aims:
• to analyse the structure, the physiological role and the distribution of OCS and antioxidant systems in
a living organism;
• to identify the reciprocal interactions of oxidant and antioxidant systems – in the general flow of
information – in a biological system (cell, tissue, organ, apparatus, system, whole organism) in a
defined step of its development, in basic conditions as well as after potentially stressful stimuli;
• to evaluate the implications of these findings by the view-point of epidemiology, patophysiology, clinics,
pharmacology and so on (30).

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The ambitious goal of redoxomics (as well as for other “-omics” in other fields) is “to map” dynamically
– by means of all the available and sophisticated analytical techniques, from electron spin resonance to
imaging – the whole oxidative-antioxidant repertoire, i. e. the “redoxoma” of a living unit in different
conditions (30).
This “integrated” approach by allowing to monitor every qualitative/quantitative changes of oxidative
balance can help the clinicians to find the optimal and “personalised” solution to correct any eventual
abnormality of redox status associated to human disease (24, 25, 30). In order to reach this goal a
specific original algorithm (31) can drive the clinician to identify the possible cause(s) and the relative
mechanism(s) (i. e. inflammation, impairment of mitochondrial respiratory function,
ischemia-reperfusion damage and pharmaco-metabolic induction) which are responsible for the
impaired oxidative balance (32–35). On the basis of the prevalent mechanism, the clinician will be able
to prescribe, in the single clinical case, a specific treatment able to reduce the increased oxidant
capacity (causative or etiological therapy) and/or to strengthen the antioxidant defences
(supplementation) (24, 31).
The prevention and/or the treatment of the diseases associated with the OS requires, besides specific
options depending on the prevalent involved mechanism, an integrated approach that Cooper (Dallas,
Texas, US) defined some years ago as the “antioxidant revolution” (36). In such a context it is very
important, after undergoing the tests, to ameliorate the life style, by adopting a healthy nutritional
model like “Mediterranean Diet” or “Okinawan Diet” that include exercise, good social relationships
and spiritual/meditation thinks (37, 38).
The American Guide Lines for Food Intake, some of which are followed by Oncologists for the
prevention of tumours, clearly suggest to take everyday from 5 to 8 portions of fruits and vegetables,
preferably fresh and in season (39). However, some Researchers prefer to this “empiric” suggestion a
more objective criteria, like that one based on the Oxygen Radical Adsorbent Capacity (ORAC) score
(40). This system is able to quantify the in vitro antioxidant capacity of all common fruits and
vegetables. For instance, 100 g of dried prunes allows an intake of 5770 ORAC UNITS. Alternatively,
the clinician can exploit the nutritional requirement found in RDA tables (recommended dietary
allowances) and LARN tables (minimal levels of recommended nutrients), which vary depending on the
geographic area, the age and the gender (41).
However, we cannot exclude that the level of food nutrients, as expected on the basis of the above
tables, is exactly the real level of the same nutrients we take when we eat a fruit or a vegetable. Indeed,
the impoverishment of the soil (due to abnormal exploitation of the soil itself, acidic rains, increasing
desertification, pollution and so on), the often uncontrolled use of pesticides, the processes of
refinement of vegetables, the processes of transformation, storage, and even the cooking of foods can
variably affect the original, as described in the above tables, antioxidant content of fruits and
vegetables (42). Therefore, as a precaution, many nutritionists today suggest the indiscriminate use of
antioxidants. However, the use of antioxidant supplements should be limited only to the documented
cases of OS, as biochemically detected by specific tests (24, 30, 43).
In this background, before suggesting any supplementation, every clinician should try to identify and
to remove the possible cause responsible for the increased production of free radicals. In particular,
reduced levels of antioxidant capacity suggest the real need of an antioxidant supplement and the
clinicians should follow some general criteria, which take into account the chemical characteristics and
the amount of the micronutrients to be proposed, the possible onset of unwanted side effects, the route
of administration, the clinical conditions of the patient, the concomitant administration of other drugs
and so on (43).
In summary, research now offers to health professionals the opportunity to identify and quantify
many markers which are currently used with the general purpose of preventing oxidative damage,

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diagnosing and monitoring OS, and evaluating the indications and effectiveness of antioxidant
supplementations and/or therapeutic interventions. Some of these markers like d-ROMs test have even
been proposed as being predictive of disease (44-46). Their potential usefulness in clinical practice is
increasing although new evidence is mandatory.
In line with these concepts it has been shown that the redox system is essential in exercise and sport
mainly due to the remarkable oxygen features. Indeed molecular oxygen was not only a fundamental
driving force of living organisms evolution but it pushed also Humans to develop – through the aerobic
metabolism – adaptive mechanisms to its handling i.e. the redox system (47).
It has been proposed that endurance running played a significant role in the evolution of Homo sapiens,
which allowed hominem, possibly from the time of Homo erectus, to hunt and obtain sufficient amounts
of meat for physical development. Based on this hypothesis, early human hunters with extreme
endurance capacity were undoubtedly highly successful. Unfortunately modern lifestyle physical
inactivity acts against the build-up of endurance capacity. And a low level of maximal oxygen uptake is a
risk factor for a number of diseases and increases the rate of mortality (47).
Probably, as a result of evolution, humans have evolved to a state where exercise-induced ROS can
stimulate elevation of the level of glucose transport to meet the need for increased metabolism. However
acute bouts of exercise, or exhaustive exercise, can elevate the oxidative damage to lipids, proteins, and
DNA and disrupt ROS-modulated signalling, which together could jeopardize cell survival. Therefore,
both acute and regular exercise can influence homeostasis, and then adaptation, which involves the
enhanced oxygen uptake-related benefits, the risk, and consequences of increased oxygen
uptake-dependent modulation of ROS production, and redox homeostasis (47).
Reactive oxygen and nitrogen species and other oxidants like hypochlorous acid, due to their
modulating activity in many metabolic processes, are constantly and physiologically produced by
muscle-skeleton system and its immune system under exercise (48).
The metabolic challenge triggered by physical exercise results in an elevated generation of ROS that
are important modulators of muscle contraction, antioxidant protection, and oxidative damage repair,
which at moderate levels generate physiological responses (47). Several factors of mitochondrial
biogenesis, such as peroxisome proliferator-activated receptor-c-coactivator 1a (PGC-1a),
mitogen-activated protein kinase, and sirtuin-1 (SIRT-1) are modulated by exercise-associated changes
in the redox milieu. PGC-1a activation could result in decreased oxidative challenge, either by
upregulation of antioxidant enzymes and/or by an increased number of mitochondria that allows lower
levels of respiratory activity for the same degree of ATP generation. Endogenous thiol antioxidants
glutathione and thioredoxin are modulated with high oxygen consumption and ROS generation during
physical exercise, controlling cellular function through redox-sensitive signaling and protein–protein
interactions. Endurance exercise-related angiogenesis, up to a significant degree, is regulated by
ROS-mediated activation of hypoxia-inducible factor 1a (47). Moreover, the exercise-associated ROS
production could be important to DNA methylation and post-translation modifications of histone
residues, which create heritable adaptive conditions based on epigenetic features of chromosomes.
Accumulating data indicate that exercise with moderate intensity has systemic and complex
health-promoting effects, which undoubtedly involve regulation of redox homeostasis and signaling
while a single bout of exhaustive exercise results in elevated levels of lipid peroxidation, carbonylation of
amino acid residues, and 8-oxo-7,8 dihydroguanine (8-oxoG) in DNA. However, when a single bout of
exhaustive exercise is given to well-trained subjects, the body responds without a large elevation in
oxidative damage (47). In addition, regular exercise training-associated adaptation is a precondition
against treatment with H2O2, which causes a significant degree of damage for untrained subjects.
Moreover, when heart attacks or strokes are simulated in untrained and trained animals, the infarct size
is significantly smaller in the trained groups, showing that regular exercise acts as a preconditioning

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tool by enhancing the adaptive zone, by narrowing the theoretical distance between functional and
biological endpoints (47). This dual effect of exercise may contribute to explain the so-called “sport
paradox” where exercise-induced ROS production can either increase or reduce human lifespan (49).
On this basis any impairment of redox system in muscles, tendons, joints and so on can lead to a
functional and/or structural impairment of muscle-skeleton system as a whole. During strong aerobic
exercise uncontrolled oxidative processes (oxidative di-stress) can take place not only in the contracting
muscle but also in the engaged connective tissue compartments, as well as in the leukocyte and
erythrocyte plasmamembranes (48). The result of this process could be: inflammation of muscles
(subclinical myositis), inflammation of connective tissues and related organs (bursitis and tendinitis),
reduced number of leukocytes and rupture of their membranes (with subsequent reduced immune
activity and increased susceptibility to infectious diseases) and haemolysis (with subsequent reduced
arterial blood oxygen content and oxygen transport capacity) (48). Any of these consequences could
result in reduced physical performance directly or indirectly in elite athletes and those enrolled in daily
fitness programs.
A wide scientific literature on Humans as well as laboratory animals supports the usefulness of
d-ROMs and BAP test in sport medicine (49-110). In particular sport amateurs and elite athletes were
shown to exhibit a lower d-ROMs test values compared to the “general population” (55). This fact likely
reflects an optimal redox functioning, a postulated consequence of the training programs. As expected
total oxidant capacity increases after exercise respect to basal values, as measured at rest. This fact
certainly reflects the increased production of oxygen free radical and their derivatives, such as
hydroperoxides, after effort, that is a well-documented consequence of strenuous aerobic activity.
However, trained individuals were shown to have lower values of d-ROMs test when compared with
non-trained peoples (which are prone to have a less efficacious antioxidant system respect to their
trained colleagues) (55). In this picture, it is interesting to note that the values of d-ROMs test directly
correlated to the intensity of exercise performed. Indeed, a highest oxidant capacity was shown after a
great endurance cycling race. Such values could indicate an alteration in health condition and may also
reveal poor recovery levels or even overtraining conditions. Finally, decreased d-ROMs test values were
observed amongst athletes taking antioxidants. This evidence confirms that specific and effective
antioxidant treatment in athletes may be important in order to compensate the alterations created
during conditions of physical stress between the production of free radicals and the efficiency of
endogenous antioxidant mechanisms.
On the basis of such evidences it is clear that d-ROMs test (together with BAP test) provides an easy
and very suitable method for clinical practice not only to prevent and to monitor the oxidative stress
but also to “personalize” training programs and antioxidant therapy either in athletes or peoples
performing training programs (55). In this picture, the values provided by d-ROMs test are related to
those of other tests evaluating oxidative balance and most importantly they were shown to be
predictive for morbidity and mortality (45, 46).
Therefore, it’s very important that all athletes and subjects practising sports at amateur levels
monitor both their OS levels by means of d-ROMs test and BAP test in order to make exercise safely
and to avoid the damage induced by the oxidative di-stress (55).
In summary, since oxidative stress causes damages to cells which may lead to an alteration of the
DNA, as seen during recent investigations, it is of vital importance that athlete who are involved in
sporting activity at amateur levels monitor their level of oxidative stress. The concomitant
determination of both d-ROMs test and BAP test can be useful in order to evaluate weather training
regimen are suitable and, thereby to improve such training and also in order to change dietary habits
and to prescribe antioxidants in cases of proven oxidative stress. Such global redox balance
measurement can be particularly interesting also to obtain an index of psycho-physical condition of an

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athlete during normal and resting period, and, therefore, the oxidative stress condition of an athlete
after a competition. In fact, high values after a race could indicate an alteration in healthy condition
and may also reveal poor recovery levels or overtraining conditions. Finally, the available data on
d-ROMs test and BAP test suggest that such approach is useful to monitor and/or to personalize the
antioxidant treatment – like BAP MINERAL (Wismerll Ltd, Tokyo, Japan) – either in athletes or in
healthy peoples. In this field further studies are in progress.
More recently oxygen infusion technique (Maya Beauty, MBE, Bologna, Italy; imported by Wismerll
Ltd, Tokyo, Japan) has been firstly introduced worldwide in Japan for sport medicine purposes in order
to prevent and to treat exercise-related OS. This non-invasive technique – previously successfully
applied in the Aesthetic Medicine – consists in the topical application of pulsed pure molecular oxygen
(94 to 98%) under pressure (2 to 3 times higher than normal atmosphere pressure). By this way
molecular oxygen should be enabled to pass transcutaneoulsy and to reach the underlying soft tissues
including muscles (111-116). Oxygen infusion may exhibit trophic, decontracting, analgesic,
anti-inflammatory, immune-modulating, and redox balancing effects thus counteracting dehydration,
overwarming, energy depletion and lactic acid accumulation for a better performance and a faster
recovery after exercise (117). Moreover oxygen propulsion is a promising curative technique in joint
disorders like osteoarthritis, meniscus and cartilage disorders and synovial membranes injuries (118).
All these effects are compatible to the ability of pure oxygen to reduce the level of hypoxia-inducible
factor 1a, thus reprogramming cell from anaerobic to aerobic metabolism (119). Clinical trials are in
progress in order to confirm such hypothesis.
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69. Francavilla G, Parisi A, Quattrocchi A, Francavilla VC, Rosa M, Cicero A, Ingallina F, Caruso A,
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