However, people often wonder whether it's healthy or unhealthy. Multiple tests can analyze metabolism. Most need blood drawn, but some can be ordered online and done at home.
Here are 2. This simple, at-home test can introduce you to your metabolic hormones. Health Conditions Discover Plan Connect. Medically reviewed by Timothy J. Legg, Ph. Effects Risk factors Prevention Takeaway Overview Oxidative stress is an imbalance between free radicals and antioxidants in your body.
Effects of oxidative stress on the body. What are the risk factors? Managing and preventing oxidative stress. The takeaway. It is worth to note that Valavanidis and colleagues [ 28 ] have already proposed 8-OHdG levels in a tissue as biomarker of oxidative stress. Of course cells can put in place several mechanisms, such as the base excision repair BER or antioxidants, as defense response against DNA lesions [ 17 — 20 ].
If not strictly controlled, oxidative stress can be responsible for the induction of several diseases, both chronic and degenerative, as well as speeding up body aging process and cause acute pathologies i. It is already well known that oxidative DNA damage is one of those stimuli responsible for cancer development [ 14 , 15 , 22 ].
Hydrolyzed DNA bases are common by-products of DNA oxidation and are considered one of the most relevant events in chemical carcinogenesis [ 14 , 22 ].
The formation of such kind of adducts impairs normal cell growth by altering the physiological transcriptomic profile and causing gene mutations. Oxidative stress can also cause a variegated amount of modifications against DNA structure, for example, base and sugar lesions, DNA-protein cross-links, strand breaks, and base-free sites. For instance, tobacco smoking, environmental pollutants, and chronic inflammation are sources of oxidative DNA damage that could contribute to tumor onset [ 14 , 17 , 29 ].
Oxidative stress resulting from lifestyle reasons can also play an important role in cancer development, as suggested by the strong correlation between dietary fat consumption a factor that exposes the organism at greater risk of lipid peroxidation and death rates from different types of cancer [ 16 , 21 ].
Cardiovascular diseases CVDs are clinical entities with a multifactorial etiology, generally associated with a very large amount of risk factors, the most broadly recognized of which are hypercholesterolaemia, hypertension, smoking habit, diabetes, unbalanced diet, stress, and sedentary life [ 11 , 30 , 31 ].
During the last years, research data pointed out that oxidative stress should be considered either a primary or a secondary cause for many CVDs [ 18 ]. Oxidative stress acts mainly as a trigger of atherosclerosis. It is well known that atheromatous plaque formation results from an early endothelial inflammation, which in turn leads to ROS generation by macrophages recruited in situ. Circulating LDL are then oxidized by reactive oxygen species, thus leading to foam cell formation and lipid accumulation.
The result of these events is the formation of an atherosclerotic plaque. Both in vivo and ex vivo studies provided evidences supporting the role of oxidative stress in atherosclerosis, ischemia, hypertension, cardiomyopathy, cardiac hypertrophy, and congestive heart failure [ 11 , 16 , 30 , 31 ].
Oxidative stress has been linked to several neurological diseases i. In AD, several experimental and clinical researches showed that oxidative damage plays a pivotal role in neuron loss and progression to dementia [ 34 ]. Several researches pointed out that lung diseases such as asthma and chronic obstructive pulmonary disease COPD , determined by systemic and local chronic inflammation, are linked to oxidative stress [ 36 — 39 ].
Oxidants are known to enhance inflammation via the activation of different kinases involving pathways and transcription factors like NF-kappa B and AP-1 [ 38 , 39 ]. Rheumatoid arthritis is a chronic inflammatory disorder affecting the joints and surrounding tissues, characterized by macrophages and activated T cell infiltration [ 15 , 40 , 41 ].
Free radicals at the site of inflammation play a relevant role in both initiation and progression of this syndrome, as demonstrated by the increased isoprostane and prostaglandin levels in synovial fluid of affected patients [ 41 ]. Oxidative stress is involved in a plethora of diseases affecting renal apparatus such as glomerulo- and tubule-interstitial nephritis, renal failure, proteinuria, and uremia [ 16 , 42 ].
The kidneys are negatively affected by oxidative stress mainly because of the fact that ROS production induces the recruitment of inflammatory cells and proinflammatory cytokine production, leading to an initial inflammatory stage. The latter stage is characterized by an increase in TGF-beta production, which orchestrates the extracellular matrix synthesis. So, when the oxidative stress stimuli act chronically on kidney tissues, the results will be an initial stage of inflammation and later the formation of abundant fibrotic tissue that impairs organ function potentially leading to renal failure.
Certain drugs, such as cyclosporine, tacrolimus, gentamycin, and bleomycin, are known to be nephrotoxics mainly because of the fact that they increase free radical levels and oxidative stress via lipid peroxidation [ 42 — 45 ]. Heavy Cd, Hg, Pb, and As and transition metals Fe, Cu, Co, and Cr , acting as powerful oxidative stress inducers, are responsible for various forms of nephropathy, as well as for some types of cancers [ 22 , 23 ].
Several authors pointed out that oxidative stress could be responsible for a delayed sexual maturation and puberty onset [ 46 , 47 ]. This seems to be true when children in prepubertal age are exposed to Cd, a well known responsible for an increase in free radicals and oxidative stress, as well as when pregnant women are exposed to the same metallic element. Summarizing, we can affirm that oxidative stress and free radicals are confirmed to be responsible for several pathological conditions affecting different tissues and systems, thus being one of the most important and pervasive harms to human health.
Human body put in place several strategies to counteract the effects of free radicals and oxidative stress, based on enzymatic e. Beside these, there are several exogenous antioxidant molecules of animal or vegetal origin, mainly introduced by diet or by nutritional supplementation. Here, we will discuss the most relevant nutritional antioxidants and their protective effects for human health.
These results were confirmed in vivo, both in mouse and rabbit models of atherosclerosis [ 53 — 55 ]. Macrophage transition to foam cells is one of the earlier and important steps in atherosclerotic lesion formation; CD36 receptor is one of the key players involved, being a scavenger receptor responsible for oxidized-LDL oxLDL uptake from bloodstream [ 56 , 57 ]. Several studies described that vitamin E is able to prevent CD36 mRNA expression induced by cholesterol, thus playing a beneficial role in preventing foam cell formation.
A degree of CD36 mRNA reduction was also observed in animals undergoing to vitamin E supplementation under a regimen of high-fat diet [ 66 — 68 ]. Each form of vitamin E seems to have different regulatory effects when it comes to recruit leukocytes to allergic inflammation site, which is however strictly dependent on vascular cell adhesion molecule-1 VCAM-1 [ 78 ]. This phenomenon was observed even in vivo, in a mouse model of allergic lung inflammation [ 80 , 81 ].
Interestingly, a research found a correlation between the prevalence of asthma and the average plasma tocopherol in several countries, based on nutritional consumption of foods and oils rich in tocopherol. Flavonoid determines i ROS synthesis suppression, inhibition of enzymes, or chelation of trace elements responsible for free radical generation; ii scavenging ROS; and iii improvement of antioxidant defenses [ , ].
Genistein is a soy isoflavone that is probably the most interesting and well-studied flavonoid compound, due to its broad pharmacological activities. Genistein has been extensively employed as antioxidant in a plethora of studies, showing the potential to scavenge ROS and RNS with a high degree of efficacy.
This flavonoid compound is able to improve the antioxidant defenses of a cell, thus prevents apoptotic process through the modulation of several genes and proteins [ ]. In nonhuman primates and rabbits [ , ], dietary-supplemented genistein delayed atherogenesis. An additional study observed an increase in antioxidant protection of LDL and an atheroprotective effect [ ].
In general, soy isoflavones confer protection against lipoprotein oxidation [ — ], as well as against oxidative DNA damage in postmenopausal women [ ], but the point is still debated [ — ]. There are other mechanism that genistein can be used to suppress oxidative stress and related inflammation in the vascular intima layer. Genistein increases the expression of antioxidant enzymes in human prostate cancer cells conferring protection against oxidative DNA damage [ , ].
Briefly, flavonoids are a class of natural compounds extensively present in foods of vegetal origin fruits, oils, seeds, etc. Nonetheless, they need to be managed carefully, and their supplementation into the diet as diet enrichment or as nutraceuticals have to take in account also some potential drawback concerning human health and wellness.
Prooxidant agents, beside their well-known detrimental effects on human health, have been investigated and, in some cases, actually used, as therapeutic agents mainly against cancer diseases. Here, we will briefly discuss two emerging prooxidant compounds showing interesting pharmacological activities, such as ascorbic acid AA and polyphenols, and the most well-known and employed prooxidant in therapy, ionizing radiation. Ascorbic acid vitamin C is a water-soluble compound classified under the group of natural antioxidants.
Ascorbate reacts with ROS, quenching them and promoting the conversion into semihydroascorbate radical, which is a poorly reactive chemical species, thus efficiently reducing the risk of cancer by suppressing free radicals and oxidative stress [ ]. Another study pointed out that AA was able to inhibit Raji cell proliferation, apparently by downregulating the set of genes needed for S-phase progression in actively proliferating cells [ ]. In an in vivo study, guinea pigs supplemented with AA at various doses showed a complete regression of fibrosarcoma and liposarcoma tumors [ ].
In general, there have been several studies assessing the antiblastic activities of AA, mostly in vitro on different cell lines [ — ].
Despite these somehow surprising but still very interesting results, there is the urge of conducting more researches, both in vitro and in vivo, to definitely assess the mode of action and efficacy of AA as prooxidative anticancer agent. Under conditions like high concentrations, high pH, and the presence of redox-active metals, phenolic compounds can acquire a prooxidant behavior [ , ], mainly based on the generation of an aroxyl radical or a labile complex with a metal cation exerting redox activity.
Polyphenols, like caffeic acid, ferulic acid, and apigenin, can exert a prooxidant effect through the increased intracellular production of ROS by NOX [ , ]. Polyphenols can as well induce oxidative stress via transition metals, promoting the generation of hydroxyl radicals through Fenton and Fenton-like reactions; it is important to note that transition metal ions are more represented into cancer than into normal cells [ ].
Prooxidant polyphenols seem to exert their cytotoxic activity by inducing apoptosis and cell cycle arrest via several pathways. Anthocyanins, pigments present in red wine and berry Aronia melanocarpa , Rosaceae, Vaccinium myrtillus , and Ericaceae fruits, cause apoptosis in cancer cells by increasing intracellular ROS formation [ — ]. Esculetin, a coumarin derivative present in plants such as chicory Cichorium intybus and Asteraceae , showed both in vivo and in vitro antiproliferative activity against hepatocellular carcinoma.
Human hepatocellular carcinoma SMMC cells incubated with esculetin undergo to mitochondrial membrane potential collapse, with Bcl-2, caspase, and caspasemediated apoptosis [ ]. In addition, esculetin also exerted a cytotoxic effect on HeLa cells inducing redox-dependent apoptosis, even in this case by causing the disruption of mitochondrial membrane potential, cytochrome C release, and caspase activation [ ].
During the last years, a very large amount of in vitro studies investigated the prooxidative effects of polyphenols against cancer cell proliferation and survival, all of them presenting interesting results that nonetheless need to be confirmed by more in-depth researches [ — ].
Although polyphenols showed the pharmacological potential to inhibit tumorigenesis and arrest cancer cell proliferation in animal models, the role of ROS generation is still poorly understood, mainly because a large majority of the in vivo studies are limited to cancer growth arrest and apoptosis evaluation, and rarely or not at all they go deeper in the mechanistic explanation of a potential prooxidant action in vivo [ , ].
The ability of ionizing radiation to counteract proliferation of cancer cells is well explained [ — ] and widely used in clinical practice.
In the last decades, there has been an extensive effort to understand the physical and molecular cellular response that follow the exposure to ionizing radiation. It is well recognized that damage to DNA operated by generation of radicals that indirectly cause DNA double-strand beaks DSBs is the most severe kind of damage induced by this prooxidant physical agent [ , ].
These lesions are promptly repaired, as the results of the rapid activation of DSB damage repair mechanism, most importantly nonhomologous end joining or homologous recombination and the execution of a complex and finely tuned sequelae of those cellular signaling pathways belonging to the DNA damage response DDR [ , ]. In the last 2 decades, several technological advancements, like intensity-modulated radiotherapy IMRT , image-guided radiotherapy IGRT , and stereotactic radiotherapy SRT , were put in place to address the need to reach that level of precision required to take advantage from radiation prooxidant activity avoiding, as much as possible, the side effects in terms of oxidative stress-induced cellular damage on healthy cells and tissues.
Oxidative stress and free radicals are generally known to be detrimental to human health. A large amount of studies demonstrates that in fact free radicals contribute to initiation and progression of several pathologies, ranging from CVD to cancer. If it is true that antioxidants can be very useful in preventing, managing, or treating human pathologies, it is true as well that they are not immune to generating adverse effects. On the other hand, some prooxidant compounds or agents can be as well useful to human health, particularly regarding cancer treatment.
We can reach to the conclusion that oxidative stress, as phenomenon, although being one of the major harms to individuals' wellness and health, it can also be exploited as a treatment tool when and if we will be able to operate a fine tuning of this process inside human organism.
The authors are thankful to all members of the Squadrito laboratory for the technical support. Gabriele Pizzino and Natasha Irrera equally contributed to this paper. National Center for Biotechnology Information , U. Oxid Med Cell Longev. Published online Jul Author information Article notes Copyright and License information Disclaimer. Received May 26; Accepted Jul 5.
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This article has been cited by other articles in PMC. Abstract Oxidative stress is a phenomenon caused by an imbalance between production and accumulation of oxygen reactive species ROS in cells and tissues and the ability of a biological system to detoxify these reactive products.
Physiological Activities of Free Radicals When maintained at low or moderate concentrations, free radicals play several beneficial roles for the organism. Detrimental Effects of Free Radicals on Human Health As stated before, if in excess, free radicals and oxidants give rise to a phenomenon known as oxidative stress; this is a harmful process that can negatively affect several cellular structures, such as membranes, lipids, proteins, lipoproteins, and deoxyribonucleic acid DNA [ 16 — 21 ].
Cardiovascular Disease and Oxidative Stress Cardiovascular diseases CVDs are clinical entities with a multifactorial etiology, generally associated with a very large amount of risk factors, the most broadly recognized of which are hypercholesterolaemia, hypertension, smoking habit, diabetes, unbalanced diet, stress, and sedentary life [ 11 , 30 , 31 ]. Neurological Disease and Oxidative Stress Oxidative stress has been linked to several neurological diseases i.
Respiratory Disease and Oxidative Stress Several researches pointed out that lung diseases such as asthma and chronic obstructive pulmonary disease COPD , determined by systemic and local chronic inflammation, are linked to oxidative stress [ 36 — 39 ].
Rheumatoid Arthritis and Oxidative Stress Rheumatoid arthritis is a chronic inflammatory disorder affecting the joints and surrounding tissues, characterized by macrophages and activated T cell infiltration [ 15 , 40 , 41 ]. Kidney Diseases and Oxidative Stress Oxidative stress is involved in a plethora of diseases affecting renal apparatus such as glomerulo- and tubule-interstitial nephritis, renal failure, proteinuria, and uremia [ 16 , 42 ].
Sexual Maturation and Oxidative Stress Several authors pointed out that oxidative stress could be responsible for a delayed sexual maturation and puberty onset [ 46 , 47 ]. Exogenous Antioxidants and Human Health Human body put in place several strategies to counteract the effects of free radicals and oxidative stress, based on enzymatic e. Prooxidant Agents in Therapy Prooxidant agents, beside their well-known detrimental effects on human health, have been investigated and, in some cases, actually used, as therapeutic agents mainly against cancer diseases.
Ascorbic Acid Ascorbic acid vitamin C is a water-soluble compound classified under the group of natural antioxidants. Polyphenols Under conditions like high concentrations, high pH, and the presence of redox-active metals, phenolic compounds can acquire a prooxidant behavior [ , ], mainly based on the generation of an aroxyl radical or a labile complex with a metal cation exerting redox activity. Radiation Therapy The ability of ionizing radiation to counteract proliferation of cancer cells is well explained [ — ] and widely used in clinical practice.
Conclusions Oxidative stress and free radicals are generally known to be detrimental to human health. Acknowledgments The authors are thankful to all members of the Squadrito laboratory for the technical support. Conflicts of Interest The authors state no conflict of interest. References 1. Sato H. Differential cellular localization of antioxidant enzymes in the trigeminal ganglion. Navarro-Yepes J. Antioxidant gene therapy against neuronal cell death.
Rajendran P. Antioxidants and human diseases. Clinica Chimica Acta. Free radicals, antioxidant defense system, and schizophrenia. Taniyama Y. Reactive oxygen species in the vasculature. Al-Gubory K. Roles of antioxidant enzymes in corpus luteum rescue from reactive oxygen species-induced oxidative stress. Reproductive Biomedicine Online. Hansen J. Nuclear and mitochondrial compartmentation of oxidative stress and redox signalling.
Annual Review of Pharmacology and Toxicology. Glasauer A. Targeting antioxidants for cancer therapy. Biochemical Pharmacology. Deponte M. Glutathione catalysis and the reaction mechanism of glutathione-dependent enzymes. Biochimica et Biophysica Acta. Halliwell B. Free Radicals in Biology and Medicine. Oxford, UK: Clarendon Press; Bahorun T. Free radicals and antioxidants in cardiovascular health and disease.
Internet Journal of Medical Update. Kumar S. Free radicals: health implications and their mitigation by herbals. British Journal of Medicine and Medical Research. Chemistry and biological activities of flavonoids: an overview. The Scientific World Journal. Valko M. Role of oxygen radicals in DNA damage and cancer incidence. Molecular and Cellular Biochemistry. Free radicals and antioxidants in normal physiological functions and human disease. Droge W. Free radicals in the physiological control of cell function.
Physiological Reviews. Willcox J. In the body, uncontrolled oxidation is typically caused by highly reactive molecules known as free radicals. Oxidation is a common chemical reaction where electrons are transferred from one molecule to another. Electrons are one of the subatomic smaller than an atom particles that make up pretty much everything. As electrons move during an oxidation reaction, bonds can be broken and the structure of the molecules changed.
Not all oxidation reactions are bad. They are essential for life and involved in many important processes. In cellular respiration , glucose a sugar from the food we eat is oxidised by oxygen from the air we breathe , producing carbon dioxide, water and energy to fuel our bodies.
Household bleaches oxidise coloured stains into colourless molecules. Free radicals are simply molecules with one or more unpaired electrons. Electrons like to be in pairs, so unpaired electrons can result in unstable and highly reactive molecules.
To become stable, the free radical must steal an electron from another molecule or give one away. When a molecule loses an electron, that molecule has been oxidised and itself becomes a free radical. Some people from racial groups may find that they age differently from others.
There are measures a person can take to reduce the signs of aging on…. A new study analyzed systemic biases against women. The authors find that societies worldwide accommodate aging men more than they do aging women.
The authors of a recently published study conclude that having higher levels of omega-3 in the blood could increase life expectancy by almost 5 years…. New research details the workings of a novel clock that relies on immune-related biomarkers to identify the risk of disease and immune well-being. How does oxidative stress affect the body? Medically reviewed by Stacy Sampson, D.
What is it? Free radicals Antioxidants Effects Conditions Risk factors Prevention Summary Oxidative stress is an imbalance of free radicals and antioxidants in the body, which can lead to cell and tissue damage. What is oxidative stress? Share on Pinterest Many lifestyle factors can contribute to oxidative stress. What are free radicals? What are antioxidants? Share on Pinterest Fresh berries and other fruits contain antioxidants.
Effects of oxidative stress. Conditions linked to oxidative stress. Risk factors for oxidative stress. Share on Pinterest Pollution can increase the risk of long-term oxidative stress.
0コメント