Open access peer-reviewed chapter. Submitted: 18 January Reviewed: 22 March Published: Appetite suppressant foods November com o cbspd.
Free radicals radicalss reactive raadicals species ROS generated from various sources in the environment as well as racicals cellular processes in the body are of serious health challenges.
Overwhelming levels of these free radicals disrupt the antioxidant defense system in the body thereby damaging cell membranes and cellular macromolecules Rple as proteins, lipids and freee acids leading to cell Rooe or ffree mutations leading to uncontrolled cell division.
Once the od antioxidant system is disrupted and kf deficient, oxidative stress emerges thereby promoting several diseases such as diabetes, arthrosclerosis, cancer, cardiovascular RRole, etc.
Because of their natural origin and therapeutic benefits, radicasl have been considered as a major source of Role of free radicals. Certain non-enzymatic plant phytochemicals frse as glutathione, polyphenols, bioflavonoids, carotenoids, freee as well as some vitamins have shown to possess antioxidant properties ffree vitro and in vivo.
These plant phytochemicals are now been used in the prevention Website performance trends management of oxidative stress-related diseases.
Man as a living creature has always indulged ardicals into several activities oc ensure his survival and well-being. In so ov, he radkcals induced the Rooe or Role of free radicals of various radicala substances or free radicals raddicals are either consumed or inhaled.
Frde, certain physiological Role of free radicals fere the Rooe generate radivals radicals or proxidants. These Role of free radicals radicals Fre reactive species, frwe of their deficiency raricals electron and instability, attack electron rich centers such as lipid RRole, proteins and nucleic acids Herbal medicine for depression damaging cells and tissues in the body.
Eventual, the human body is adapted to radicalx these unstable molecules by a fere of molecules including certain enzymes collectively known as antioxidants. This antioxidant radicalss system raidcals the level of these free radicals in Roel body and maintains the homeostatic balance for proper functioning frde the body.
However, when these reactive species are overwhelming radocals in the body, it surpasses the capacity of the antioxidant og system leading to radiacls condition known as oxidative stress.
This radkcals between antioxidant and proxidants is characteristic of gadicals disease conditions such as diabetes, Role of free radicals, cardiovascular diseases, cancer Improve metabolism for better nutrient absorption. One of the radicaks remedy for this condition is to supplement the endogenous antioxidant defense system with exogenous antioxidants.
Plants have gained considerable interest in recent time in managing oxidative stress radiccals diseases; firstly, because of their ethnopharmacological uses in Rple diseases and secondly, due to Roe richness in phytochemicals radicale possess radicwls properties.
Hence, this chapter frre aimed gadicals give an overview Nootropic for Cognitive Performance Role of free radicals radicals, their sources of origin and processes of generation in the environment and body.
Also, it will highlight on the various mechanisms of free radical induced cellular fo and the associated diseases due to oxidative stress. The various Lower cholesterol with heart-healthy fats of the antioxidant defense system; both enzymatic and non-enzymatic antioxidants will free described as Raidcals as the contribution of plant free as antioxidants.
Emphasis radicqls be laid on some plants and phytochemicals freee antioxidant rdaicals stating ravicals mode of scavenging free radicals and prevention of oxidative stress-related diseases. Free radicals are molecular species with Rope electrons in their atomic orbital frre of independent existence.
Rope such, these radicals are highly reactive and can either Rooe an electron from molecules or donate an electron to other molecules thus acting as a reductant or an oxidant.
Some oxygen species known as reactive oxygen Natural chlorogenic acid ROS are raicals in their natural state gree are capable of generating free Rile.
The idea of free fgee began fo chemistry around the beginning od the twentieth century, where chemists initially described them RRole intermediate organic and inorganic fre with several suggested freee. A clear understand of these radicals rzdicals then proposed based on the work of Daniel Gilbert and Rebecca Gersham Rle [ 2 ] in which radcals radicals were suggested to play important roles in biological environments but oof responsible for certain deleterious processes in the cell.
Thereafter byHerman Denham further suggested that these reactive species may play critical roles in physiological process radical aging radicaals [ rqdicals ].
This hypothesis on raducals theory of free-radical on Organic mood management, inspired numerous fre and frwe which radicaals contributed racicals the understanding of radicals and other related species such radicalw ROS, reactive oof species RNS raficals non-radical reactive species [ 4 ].
ROS are classified into two major categories of compounds which includes the free radicals and the non-reactive radicals. These species are considered as free radicals since they contain at least one unpaired electron in the shells around the atomic nucleus which makes them unstable and therefore can easily donate or obtain another electron to attain stability.
As such, they are highly reactive and capable of independent existence [ 67 ]. On the other hand, the non-reactive radicals are a group of compounds which are not radicals but are extremely reactive or can easily be converted to reactive species.
Examples of these substances include hypochlorous acid HClOhydrogen peroxide H 2 O 2organic peroxides, aldehydes, ozone O 3and O 2 as shown in Table 1.
As reviewed from Sultan [ 8 ], free radicals can originate either from the environment, physiological processes or endogenous sources. External sources: Certain organic compounds in the atmosphere can react non-enzymatically with oxygen to generate free radicals.
Also, reactions initiated by ionizing radiations in the environment can generate free radicals. Thus, some external sources of free radicals include environmental pollutant, cigarette smoke, alcohol, radiations, ozone, ultraviolet light, pesticides, anesthetic, certain drugs, industrial solvents etc.
Endogenous sources: This includes processes in living organisms that necessitates enzymatic reactions to generate free radicals. These include reactions involved in the respiratory chain, cytochrome P system, phagocytosis and prostaglandin synthesis.
Some of these endogenous sources of free radicals generation include reactions in the mitochondria, phagocytes, inflammation, arachidonate pathways, etc. Also, reactions involving iron and other transition metals, peroxisomes, xanthine oxidase, etc. are also endogenous sources of free radicals.
Physiological sources: Certain physiological state or processes like stress, emotion, aging, etc. mental status and disease conditions are also responsible for the formation of free radicals. For example, hyperglycemia is a major source of free radicals in diabetes patients through various metabolic pathways which include increase flux of glucose through the polyol pathway, increase formation of advanced glycation end-products AGEs and activation of their receptors, activation of protein kinase C PKC isoforms, activation of overactivity of hexosamine pathway and decrease antioxidant defense [ 9 ].
Free radicals are generated through various physiological processes in living organisms. Once generated, they can react with other biomolecules to attain stability. In living systems, superoxide can be generated through several mechanisms [ 10 ].
Several molecules such as flavine nucleotides, adrenaline, thiol compounds, glucose, etc. can be oxidized in the presence of oxygen to generate superoxide and these reactions are greatly accelerated by the presence of transition metals such as iron or copper.
During the electron transport chain in the inner mitochondrial membrane, oxygen is reduced to water thereby producing free radical intermediates that subsequently reacts with free electrons to produce superoxide [ 11 ].
Certain reactions by enzymes such as cytochrome p oxidase in the liver releases free electrons that can react with oxygen to produce superoxide.
Other enzymes can neutralize nitric oxide thereby producing superoxide [ 12 ]. Also, phagocytic cells during respiratory burst can generate superoxide [ 13 ]. Hydrogen peroxide H 2 O 2 : Hydrogen peroxide is mostly produced from the spontaneous dismutation reaction of superoxide in biological systems.
Also, several enzymatic reactions including those catalyzed by D-amino acid and glycolate oxidases can directly produce H 2 O 2 [ 14 ]. Generally, H 2 O 2 is not a free radical but it is considered as a reactive oxygen species ROS because it can be transformed to other free radicals such as hydroxyl radical which mediate most of the toxic effects ascribed to H 2 O 2.
Myeloperoxidase can decompose H 2 O 2 into singlet oxygen and hypochlorous acid, a mechanism which phagocytes utilize to kill bacteria [ 15 ].
However, H 2 O 2 is a weak oxidizing agent that might directly damage enzymes and proteins which contain reactive thiol groups. One of the most vital properties of H 2 O 2 over superoxide is its ability to freely traverse cell membranes [ 16 ].
Most ROS are usually converted to hydroxyl radical. Thus, it is usually the final mediator of most free radical induced tissue damage [ 17 ]. Hydroxyl radical is generated by various mechanisms but the most important is the in vivo mechanism due to decomposition of superoxide and hydrogen peroxide catalyzed by transition metals [ 18 ].
Transition metals generally contain one or more unpaired electrons and thus are capable to transfer a single electron. Iron and copper are the most common transition metals capable of generating free radicals and much implicated in human diseases.
As shown by Fenton [ 19 ], hydrogen peroxide can react with iron II or copper I to generate hydroxyl radical:. L-arginine and L-citrulline are both converted to nitric oxide. Nitric oxide can further react with superoxide to form peroxynitrite.
Protonated form of peroxynitrite ONOOH acts as a powerful oxidizing agent to sulfhydryl SH groups thereby causing oxidation of many molecules and proteins leading to cellular damage [ 20 ]. It can also cause DNA damage such as breaks, protein oxidation and nitration of aromatic amino acid residues in proteins.
Reactive oxygen species and their oxidative stress induced damaged is summarized in Figure 1. Reactive oxygen species ROS -induced oxidative damage. Source: Kohen and Nyska [ 21 ]. Continual influx and generation of ROS from endogenous and exogenous sources lead to oxidative damage of cellular components and may impair many cellular functions [ 22 ].
The most vulnerable biological targets to oxidative damage include proteins, enzymes, lipidic membranes and DNA [ 5 ]. Lipids: All cellular membranes are generally vulnerable to oxidative damage since they are highly rich in unsaturated fatty acid.
The lipid damage due to ROS usually known as lipid peroxidation occurs in three stages [ 23 ]. The first stage, known as initiation involves the attack of a reactive oxygen metabolite capable of abstracting a hydrogen atom from a methylene group in the lipid due to the presence of a weak double bond.
As such, the remaining fatty acid radical retains one electron and stabilizes by rearrangement of the molecular structure to form a conjugated diene. These propagation reactions occur repeatedly leading to the peroxidation of several unsaturated lipid in the membrane.
Hydrogen peroxide and superoxide radicals have weak effects on proteins except for proteins containing SH groups. Following interaction with ROS, proteins can undergo direct damages such as damaging specific amino acid residues and changing their tertiary lf and indirect damages such as peroxidation, degradation and fragmentation.
The consequences of protein damage include loss of enzymatic activity and altered cellular functions. Protein oxidation products are usually keto, aldehydes and carbonyls compounds. Following protein oxidation, proteins are susceptible to many changes in their function which include inactivation, chemical fragmentation and increased proteolytic degradation [ 24 ].
Nucleic acid: Though DNA is a stable molecule, ROS can interact with it to cause several types of damages which include double- and single- DNA breaks, modification of DNA bases, loss of purines apurinic sitesDNA-protein cross-linkage, damage to the deoxyribose sugar and damage to the DNA repair system.
Hydroxyl radical is the most detrimental ROS that affects nucleic acids [ 25 ]. Also, hydroxyl radicals can attack pyrimidines leading to the formation of thymine peroxide, thymine glycols, 5- hydroxymethyl uracyl, and other such products. When the concentration of ROS exceeds those of antioxidant neutralizing species, a condition known as oxidative stress occurs.
As reviewed from Rahman et al. Evidence via monitoring biomarkers such as the presence of ROS and RNS as well as antioxidant defense has indicated oxidative damage may be implicated in the pathogenesis of these diseases [ 29 ].
Oxidative stress also contributes to tissue injury following hyperoxia and irradiation. Evidence from studies have shown oxidative stress to play an important role in the pathogenesis and development of metabolic syndrome related disorders such as obesity, hypertension, diabetes, dyslipidemia etc.
as well as in cardiovascular related diseases such as myocardial infarction, aortic valve stenosis, angina pectoris, atherosclerosis and heart failure [ 32333435 ].
Cancer is another disease associated with ROS as ROS have been suggested to stimulate oncogenes such as Jun and Fos whose overexpression is directly associated with lung cancer [ 36 ].
In lung cancers, p53 can be mutated by ROS thereby losing its function of apoptosis and functioning as an oncogene [ 37 ]. Also, the development of gastric cancer has been thought to be due to increase production of ROS and RNS by Helicobacter pylori infection in human stomach [ 29 ].
: Role of free radicals| Introduction | The basic causes include the following. Normally, bonds do not split to leave a molecule with an odd and an unpaired electron. But when weak bonds split, free radicals are formed. Free radicals are very unstable and react quickly with other compounds, trying to capture the needed electron to gain stability. When the "attacked" molecule loses its electron, it becomes a free radical itself, beginning a chain reaction. All this happens in nanoseconds. Once the process is started, it can cascade, finally resulting in the disruption of a living cell. Normally, the body can handle free radicals, but if antioxidants are unavailable, or if the free radical production becomes excessive, damage can occur. In chemistry, free radicals take part in radical addition and radical substitution as reactive intermediates. Chain reactions involving free radicals can usually be divided into three distinct processes:. Initiation reactions are those, which result in a net increase in the number of free radicals. They may involve the formation of free radicals from stable species or they may involve reactions of free radicals with stable species to form more free radicals. Propagation reactions involve free radicals in which the total number of free radicals remains the same. Termination reactions are those reactions resulting in a net decrease in the number of free radicals. The formation of radicals may involve breaking of covalent bonds homolytically, a process that requires significant amounts of energy. The bond energy between two covalently bonded atoms is affected by the structure of the molecule. Homolytic bond cleavage most often happens between two atoms of similar electronegativity. However, propagation is a very exothermic reaction. Radicals may also be formed by single electron oxidation or reduction of an atom or molecule. An example is the production of superoxide by the electron transport chain. Peroxidation of lipids in cell membranes can damage cell membranes by disrupting fluidity and permeability. Lipid peroxidation can also adversely affect the function of membrane bound proteins such as enzymes and receptors. Direct damage to proteins can be caused by free radicals. This can affect many kinds of protein, interfering with enzyme activity and the function of structural proteins. Fragmentation of DNA caused by free radical attack causes activation of the poly ADP-ribose synthetase enzyme. The site of tissue damage by free radicals is dependent on the tissue and the reactive species involved. Extensive damage can lead to death of the cell; this may be by necrosis or apoptosis depending on the type of cellular damage. When a cell membrane or an organelle membrane is damaged by free radicals, it loses its protective properties. This puts the health of the entire cell at risk. Cells normally defend themselves against ROS damage through the use of enzymes such as superoxide dismutase and catalase. Small molecule antioxidants such as ascorbic acid vitamin C , uric acid, and glutathione also play important roles as cellular antioxidants. Similarly, polyphenol antioxidants assist in preventing ROS damage by scavenging free radicals. The negative effects of ROS on cell metabolism include roles in programmed cell death and apoptosis, whereas positive effects include induction of host defense genes and mobilization of ion transport systems. In particular, platelets involved in wound repair and blood homeostasis release ROS to recruit additional platelets to sites of injury. These also provide a link to the adaptive immune system via the recruitment of leukocytes. Reactive oxygen species are involved in cardiovascular disease, hearing impairment via cochlear damage induced by elevated sound levels, ototoxicity of drugs such as cisplatin, and in congenital deafness in both animals and humans. Reactive oxygen species ROS are very small molecules and are highly reactive due to the presence of unpaired valence shell electrons. ROS is formed as a natural byproduct of the normal metabolism of oxygen and have important roles in cell signaling. However, during times of environmental stress ROS levels can increase dramatically, which can result in significant damage to cell structures. Platelets involved in wound repair and blood homeostasis release ROS to recruit additional platelets to sites of injury. Generally, harmful effects of reactive oxygen species on the cell are most often like -Damage of DNA, oxidations of polydesaturated fatty acids in lipids, oxidations of amino acids in proteins, oxidatively inactivates specific enzymes by oxidation of co-factors Table 1. Transferin iron Vitamin C, Ferritin iron beta-carotene, Myoglobin iron. Thiols GSH, Lipoic acid, N-acetyl cysteine NADH and NADPH Ubiquinone. Table 1 Reactive oxygen species and their corresponding neutralising antioxidants and also additional antioxidants These are the list of antioxidants that help to include in the diet and manage to scavenge the free radical that can develop the steps of neurodegeneration. All aerobic forms of life maintain elaborate anti-free-radical defense systems, also known as antioxidant systems. Enzymes: The defense enzyme, superoxide dismutase SOD , takes hold of molecules of superoxide—a particularly destructive free radical-and changes them to a much less reactive form. SOD and another important antioxidant enzyme set, the glutathione system, work within the cell. Self repair: The body also has systems to repair or replace damaged building blocks of cells. Most protein constituents in the cell are completely replaced every few days. Scavenger enzymes break used and damaged proteins into their component parts for reuse by the cell. Nutrients: Vitamins and other nutrients neutralize the oxy radicals' and serves as second line of defense. Among the many substances used are Vitamins C and E, beta-carotene, and bioflavonoids. Free radical or oxidative injury may be a fundamental mechanism underlying a number of human neurologic diseases. OS can cause cellular damage and subsequent cell death because the reactive oxygen species ROS oxidize vital cellular components such as lipids, proteins, and DNA. Therapy using free radical scavengers antioxidants has the potential to prevent, delay, or ameliorate many neurologic disorders. However, the biochemistry of oxidative pathobiology is complex, and optimum antioxidant therapeutic options may vary and need to be tailored to individual diseases. In vitro and animal model studies support the potential beneficial role of various antioxidant compounds in neurologic disease. However, the results of clinical trials using various antioxidants, including vitamin E, tirilazad, N-acetylcysteine, and ebselen, have been mixed. Moreover, therapy with antioxidants may need to be given early in chronic insidious neurologic disorders to achieve an appreciable clinical benefit. Pre-disease screening and intervention in at-risk individuals may also need to be considered in the near future. Oxidative stress is a general term used to describe a serious imbalance between the production of reactive oxygen species ROS and reactive nitrogen species RNS on the one hand, and the levels of antioxidant defences on the other. Any prolonged imbalance results in oxidative damage to cells, tissues, and organs. External sources of ROS include radiation, UV light, chemical reagents, pollution, cigarette smoke, drugs of abuse, and alcohol. At low or moderate levels, ROS and RNS exert beneficial effects on cellular responses and immune function. However, at high concentrations, they cause oxidative stress, and subsequent damage to proteins, lipids, and DNA. Why the need of the free radical in neurodegeneration: The harmful effects of ROS cause damage to macromolecules such as proteins, lipids, polysaccharides or nucleic acids, are termed oxidative stress. The intrinsic properties of neurons make them highly vulnerable to the detrimental effects of ROS: high metabolic rates; a rich composition of fatty acids prone to peroxidation; high intracellular concentrations of transition metals, capable of catalyzing the formation of reactive hydroxyl radicals; low levels of antioxidants; and reduced capability to regenerate. Neurons have intense energy demands which are met by mitochondria. Mitochondria are both targets and important sources of ROS. It has been shown that oxidative stress stimulates mitochondrial fission; the addition of hydrogen peroxide to cultured cerebellar granule neurons induced mitochondrial fragmentation within one hour of treatment. It was also shown that nitric oxide causes increased mitochondrial fission in neurons, prior to the onset of neuronal loss in a mouse model of stroke. On the other hand, expression of Mfn or a dominant negative Drp1 in cultured neurons, was protective against oxidative insults. The generation of ROS appears to be increased in damaged mitochondria, and in cells with compromised mitochondrial function. Oxidative stress within mitochondria can lead to a vicious cycle in which ROS production progressively increases leading, in turn, to progressive augmentation of damage. Nucleic acid oxidation occurs in neurons during disease and is detected as elevated levels of 8-hydroxydeoxyguanosine 8-OHDG in DNA and 8-hydroxyguanosine in RNA. Hydroxyl radical-mediated DNA damage often results in strand breaks, DNA-protein crosslinking, and base-modifications. All of these events can lead to neuronal injury. It is known that generation of ROS results in an attack not only on DNA, but also on other cellular components involving polyunsaturated fatty acid residues of phospholipids, which are extremely sensitive to oxidation. Once formed, peroxyl radicals ROO· can be rearranged via a cyclisation reaction to endoperoxides precursors of malondialdehyde with the final product of the peroxidation process being malondialdehyde MDA. The major aldehyde product of lipid peroxidation other than malondialdehyde is 4-hydroxynonenal HNE. Increased production of ROS also results in protein oxidation. Oxidation of cysteine residues may lead to the reversible formation of mixed disulfides between protein thiol groups —SH and low molecular weight thiols, in particular glutathione GSH, S-glutathiolation. The concentration of carbonyl groups, generated by many different mechanisms is a good measure of ROS-mediated protein oxidation. The generation of isoprostanes has been shown to be a sensitive measure of lipid peroxidation, which are increased in cerebrospinal fluid CSF of HD patients. ROS are often present in brain regions affected by neurodegenerative diseases. Studies in both HD patients and experimental models of HD support a role for oxidative stress and ensuing mitochondrial dysfunction in mediating the neuronal degeneration observed in HD. Oxidative damage in HD has been previously reviewed in detail. The accumulation of ROS in neurons, and subsequent oxidative stress are attenuated by free radical scavengers, which can be categorized as enzymatic or non-enzymatic antioxidants. Enzymatic antioxidants constitute one of the defense mechanisms against free radicals. These include superoxide dismutase SOD , glutathione peroxidase Gpx and catalase CAT. Non-enzymatic antioxidants are represented by ascorbic acid Vitamin C , α-tocopherol Vitamin E , glutathione GSH , retinoic acid, carotenoids, flavonoids, and other antioxidants. The therapeutic approaches tested in vitro or in toxin or transgenic models of HD are given below-. As we know that neurodegenerative disorders is an important source of morbidity and mortality in human mankind. Free radical involvement offers a novel therapeutic target in the management of Huntington diseases. However, it will happen only if the mechanism of action of the free radical can be understood properly. The antioxidant therapy can be used over the free radical generation and target the free radical that are responsible for the neurodegeneration such as HD. Free-radical-mediated oxidative injury plays a major role in the defection of various diseases and trauma; chronic neurogenic and other neurodegeneration disease can be recognized. We know that oxygen is an essential molecule for survival of majority of living organisms in the world as well as the inside the body. Oxidative stress mostly a harmful condition that occurs when there is an excess of free radicals will be generated or a decrease in antioxidant levels in the body. So, this review suggests the use of antioxidants to manage the disease state. Antioxidants quench oxidative stress by 1working to off-pair free radical generation and stopping them from starting the chain reactions that contribute to develop Huntington disease. Oxidative stress OS has been responsible in the pathophysiology of various life threatening starts disease such as neurological and neurodegenerative diseases. Oxygen Species generally a free radical species can cause cellular damage and subsequent cell death because the reactive oxygen species which oxidize sensitive cellular components that makes a major part of proteins, lipids, ribose sugar and genetic material. However, the excitatory amino acid glutamate is the major amino acid that can prevent such kind of neurodegeneration that are responsible for Huntington disease populations that are at high risk, such as elderly and newly diagnosed patients. In this review we have to find the new way and the use of certain antioxidants to remove the wastes of free radical generation and scavenging properties of the antioxidants to manage in the disease and cure them. This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially. About Us Paper Submission FAQs Testimonials Videos Reprints Pay Online Article Processing Charges Contact Us Sitemap. Home Open Access Journals eBooks Information For Author Article Processing Charges. Publication Ethics. Peer Review System. Behavioral Sciences Food and Nutrition Trends Global Trends in Pharmaceutical Sciences. Home JAPLR Role of free radicals and certain antioxidants in the management of huntingtons disease a review. Journal of. Review Article Volume 7 Issue 4. Types of long lived radicals Stable radicals : The prime example of a stable radical is molecular oxygen O 2. Formation of free radicals Normally, bonds do not split to leave a molecule with an odd and an unpaired electron. Chain reactions involving free radicals can usually be divided into three distinct processes: Initiation, Propagation, Termination. Lipids Peroxidation of lipids in cell membranes can damage cell membranes by disrupting fluidity and permeability. Proteins Direct damage to proteins can be caused by free radicals. DNA Fragmentation of DNA caused by free radical attack causes activation of the poly ADP-ribose synthetase enzyme. Oxidative stress Oxidative stress is a general term used to describe a serious imbalance between the production of reactive oxygen species ROS and reactive nitrogen species RNS on the one hand, and the levels of antioxidant defences on the other. The therapeutic approaches tested in vitro or in toxin or transgenic models of HD are given below- In vitro studies Metalloporphyrins, metal-containing catalytic antioxidants, have emerged as a novel class of potential therapeutic agents that scavenge a wide range of reactive oxygen species. A manganese porphyrin has been reported to significantly reduce cell death in an in vitro chemical model of HD. Treating cultured rodent cortical neurons with glutamate resulted in significant neurodegeneration, which was completely rescued with ascorbic acid co-treatment. Using a neuronal cell-based assay, glutamate-induced neuronal death was significantly attenuated in a dose-dependent manner by α-tocopherol. Also, treatment with idebenone in this in vitro model resulted in complete neuroprotection in a dose-dependent manner. Melatonin significantly reduced DNA damage and improved neuronal survival. In another study using the 3-NP model of HD, melatonin treatment significantly ameliorated the increase in lipid peroxidation, protein carbonyls and SOD activity within the striatum. Selenium dose-dependently reduced lipid peroxidation and significantly improved neuronal morphology within the striatum of rats treated with quinolinic acid, an N-methyl-D-aspartate antagonist that results in striatal neurodegeneration. Creatine also buffers intracellular energy reserves through its intermediate, phosphocreatine PCr ; stabilizes intracellular calcium; and inhibits activation of the mitochondrial transition pore. Creatine supplementation significantly reduces striatal lesion volumes produced by the neurotoxins 3-NP and malonate. The antioxidant compound CoQ10 also demonstrated efficacy in murine models of HD. CoQ10, ubiquinone, is a lipid-soluble benzoquinone which, when reduced to ubiquinol, which possesses significant antioxidant potential. In addition, CoQ10 can induce increases in vitamin E, enhancing its antioxidant capacity. Using the mitochondrial toxins malonate. FK also known as Tacrolimus or Fujimycin is an immunosuppressive drug mainly used to lower allograft rejection and also in topical preparations. Recently, the neuroprotective effects of FK were reported in 3-NP model of HD. FK treatment significantly reduced behavioral deficits, MDA levels, nitrite concentration, and restored antioxidant enzyme levels of SOD and catalase, and levels of dopamine and norepinephrine in the striatum, cortex, and hippocampus. Lycopene, a carotenoid pigment and phytochemical naturally found in fruits and vegetables, reduced oxidative stress markers and improved behavior in a 3-NP induced rodent model of HD. In transgenic mouse models of HD Lipoic acid is an essential cofactor for many enzyme complexes and is present in mitochondria as the cofactor for pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase. It is an effective antioxidant and has been used to treat disease associated with impaired energy metabolism. Pyruvate plays a major role in glycolysis, and also possesses significant antioxidant capacity. Creatine exists in the cell both as free creatine and phosphocreatine PCr which together comprise the total creatine pool. In tissues with high energy requirements such as skeletal muscle and brain, PCr serves as a short term energy buffer in which adenosine diphosphate is phosphorylated to adenosine triphosphate. This phosphorogroup transfer is catalyzed by the important creatine kinase CK enzyme. It is effective in preventing cell membrane damage caused by reactive oxygen species. Recently, administration of a relatively high dose of L-carnitine to NQ transgenic mice was shown to extend the survival, ameliorate motor performance, and decrease the number of intranuclear aggregates. Synthetic triterpenoids, which are analogues of 2-Cyano-3, Dioxooleana-1,9-DienOic acid CDDO , are of great interest because of their antioxidant and anti-inflammatory properties. Triterpenoids significantly preserved the striatal volumes of the NQ mice, by preventing the atrophy of the medium spiny neurons, and they rescued behavioral deficits, extended survival, attenuated peripheral pathology, and reduced 8-OHdG, MDA and 3-nitrotyrosine immune-reactivity in the striatum. The Huntington's Disease Collaborative Research Group. A novel gene containing a rinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Ross CA, Tabrizi SJ. Huntington's disease: from molecular pathogenesis to clinical treatment. Lancet Neurol. Roze E, Bonnet C, Betuing S, et al. Huntington's disease. Adv Exp Med Biol. Rosas HD, Salat DH, Lee SY, et al. Complexity and heterogeneity: what drives the ever—changing brain in Huntington's disease? Ann NY Acad Sci. Cowan CM, Raymond LA. Discrimination at work is linked to high blood pressure. Icy fingers and toes: Poor circulation or Raynaud's phenomenon? Some vitamins and minerals — including vitamins C and E and the minerals copper, zinc, and selenium — serve as antioxidants, in addition to other vital roles. Because free radicals lack a full complement of electrons, they steal electrons from other molecules and damage those molecules in the process. Antioxidants neutralize free radicals by giving up some of their own electrons. In making this sacrifice, they act as a natural "off" switch for the free radicals. This helps break a chain reaction that can affect other molecules in the cell and other cells in the body. But it is important to recognize that the term "antioxidant" reflects a chemical property rather than a specific nutritional property. While free radicals are damaging by their very nature, they are an inescapable part of life. The body generates free radicals in response to environmental insults, such as tobacco smoke, ultraviolet rays, and air pollution, but they are also a natural byproduct of normal processes in cells. When the immune system musters to fight intruders, for example, the oxygen it uses spins off an army of free radicals that destroy viruses, bacteria, and damaged body cells in an oxidative burst. Some normal production of free radicals also occurs during exercise. This appears to be necessary in order to induce some of the beneficial effects of regular physical activity, such as sensitizing your muscle cells to insulin. Because free radicals are so pervasive, you need an adequate supply of antioxidants to disarm them. Your body's cells naturally produce some powerful antioxidants, such as alpha lipoic acid and glutathione. The foods you eat supply other antioxidants, such as vitamins C and E. Plants are full of compounds known as phytochemicals—literally, "plant chemicals"—many of which seem to have antioxidant properties as well. For example, after vitamin C has "quenched" a free radical by donating electrons to it, a phytochemical called hesperetin found in oranges and other citrus fruits restores the vitamin C to its active antioxidant form. Carotenoids such as lycopene in tomatoes and lutein in kale and flavonoids such as flavanols in cocoa, anthocyanins in blueberries, quercetin in apples and onions, and catechins in green tea are also antioxidants. News articles, advertisements, and food labels often tout antioxidant benefits such as slowing aging, fending off heart disease, improving flagging vision, and curbing cancer. And laboratory studies and many large-scale observational studies those that query people about their eating habits and supplement use and then track their disease patterns have noted antioxidant benefits from diets rich in them, particularly those coming from a broad range of colorful vegetables and fruits. But results from randomized controlled trials of antioxidant supplements in which people are assigned to take specific nutrient supplements or a placebo have not supported many of these claims. Indeed, too much of these antioxidant supplements won't help you and may even harm you. It is better to supply your antioxidants from a well-rounded diet. To learn more about the vitamins and minerals you need to stay healthy, read Making Sense of Vitamins and Minerals , a Special Health Report from Harvard Medical School. As a service to our readers, Harvard Health Publishing provides access to our library of archived content. Please note the date of last review or update on all articles. No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician. Thanks for visiting. Don't miss your FREE gift. The Best Diets for Cognitive Fitness , is yours absolutely FREE when you sign up to receive Health Alerts from Harvard Medical School. |
| Role of free radicals in human inflammatory diseases | Depleted nitrite and enhanced oxidative stress in urolithiasis. Increased ROS levels modulate transcription factor activity, especially NF-κB, activator protein-1 AP-1 and the peroxisome proliferators-activated receptor PPAR family of transcriptional activators Elahi et al. Direct damage to proteins can be caused by free radicals. Liposoluble antioxidants, fat-soluble antioxidants are those that are absorbed in the presence of fats. Cell Free Radic. |
| REVIEW article | Effect of puerarin in promoting fatty acid oxidation by increasing mitochondrial oxidative capacity and biogenesis in skeletal muscle in diabetic rats. Also, reactions involving iron and other transition metals, peroxisomes, xanthine oxidase, etc. Home About Cancer Cancer Causes and Prevention Risk Factors Diet Antioxidants and Cancer Prevention. Neurobiology of Aging. Banafsheh, A. Ascorbic acid Vitamin C : Ascorbic acid is a water-soluble antioxidant. |
| We Care About Your Privacy | Antioxidants neutralize free radicals by giving up some of their own electrons. In making this sacrifice, they act as a natural "off" switch for the free radicals. This helps break a chain reaction that can affect other molecules in the cell and other cells in the body. But it is important to recognize that the term "antioxidant" reflects a chemical property rather than a specific nutritional property. While free radicals are damaging by their very nature, they are an inescapable part of life. The body generates free radicals in response to environmental insults, such as tobacco smoke, ultraviolet rays, and air pollution, but they are also a natural byproduct of normal processes in cells. When the immune system musters to fight intruders, for example, the oxygen it uses spins off an army of free radicals that destroy viruses, bacteria, and damaged body cells in an oxidative burst. Some normal production of free radicals also occurs during exercise. This appears to be necessary in order to induce some of the beneficial effects of regular physical activity, such as sensitizing your muscle cells to insulin. Because free radicals are so pervasive, you need an adequate supply of antioxidants to disarm them. Your body's cells naturally produce some powerful antioxidants, such as alpha lipoic acid and glutathione. The foods you eat supply other antioxidants, such as vitamins C and E. Plants are full of compounds known as phytochemicals—literally, "plant chemicals"—many of which seem to have antioxidant properties as well. For example, after vitamin C has "quenched" a free radical by donating electrons to it, a phytochemical called hesperetin found in oranges and other citrus fruits restores the vitamin C to its active antioxidant form. Carotenoids such as lycopene in tomatoes and lutein in kale and flavonoids such as flavanols in cocoa, anthocyanins in blueberries, quercetin in apples and onions, and catechins in green tea are also antioxidants. News articles, advertisements, and food labels often tout antioxidant benefits such as slowing aging, fending off heart disease, improving flagging vision, and curbing cancer. And laboratory studies and many large-scale observational studies those that query people about their eating habits and supplement use and then track their disease patterns have noted antioxidant benefits from diets rich in them, particularly those coming from a broad range of colorful vegetables and fruits. But results from randomized controlled trials of antioxidant supplements in which people are assigned to take specific nutrient supplements or a placebo have not supported many of these claims. Indeed, too much of these antioxidant supplements won't help you and may even harm you. It is better to supply your antioxidants from a well-rounded diet. To learn more about the vitamins and minerals you need to stay healthy, read Making Sense of Vitamins and Minerals , a Special Health Report from Harvard Medical School. As a service to our readers, Harvard Health Publishing provides access to our library of archived content. Please note the date of last review or update on all articles. No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician. Thanks for visiting. Don't miss your FREE gift. The Best Diets for Cognitive Fitness , is yours absolutely FREE when you sign up to receive Health Alerts from Harvard Medical School. Sign up to get tips for living a healthy lifestyle, with ways to fight inflammation and improve cognitive health , plus the latest advances in preventative medicine, diet and exercise , pain relief, blood pressure and cholesterol management, and more. Get helpful tips and guidance for everything from fighting inflammation to finding the best diets for weight loss from exercises to build a stronger core to advice on treating cataracts. PLUS, the latest news on medical advances and breakthroughs from Harvard Medical School experts. In , Denham Harmon proposed the free radical theory of aging. In , McCord and Fridovich discovered superoxide dismutase. On the other hand, some research groups have discovered the involvement of free radicals in the fight against infection as part of the cellular immune response, where ROS and Reactive Nitrogen Species RNS act together with reactive halogen species to fight invading microorganisms. Halliwell and Gutteridge reported in that ROS include both free-radical and non-radical oxygen derivatives. Acute inflammation is a short procedure that lasts from minutes to several days. The main signs of acute inflammation are the leakage of plasma proteins or fluid and the movement of leukocytes into the extravascular area. These cellular and vascular responses are mediated by cell or plasma-derived chemical factors and are responsible for the classic clinical symptoms of inflammation, such as swelling, redness, pain, heat, and loss of function. Although an inflammatory response can occur to any noxious stimulus, the characteristic of this process is the response of vascularized connective tissue. Inflammation is a vital response of the human immune system. Chronic inflammation can have several secondary biological response effects associated with increased risk of chronic diseases and disorders. They can also occur with physical or chemical substances that cannot be broken down, as well as with some genetic susceptibility. Persistence of foreign bodies, continuous exposure to chemicals, recurrent acute inflammation, or specific pathogens is all crucial causes of chronic inflammation. The molecular and cellular process of chronic inflammation depends on the type of inflamed cells and organ. Reactive Oxygen Species ROS : In a living system, the most important radicals are those derived from oxygen, and these are called reactive oxygen species. ROS are formed as products of normal physiological conditions due to the partial reduction of molecular oxygen. ROS can be generated from several endogenous sources, such as xanthine oxidase, cytochrome oxidase, cyclooxygenase, mediated oxidation of unsaturated fatty acids, catecholamine oxidation, mitochondrial oxidation, inflammation, phagocytosis, ischemia reperfusion injury, leukocyte activation of nicotinamide adenine dinucleotide phosphate oxidase, iron release, and the redox reaction. Hydrogen peroxide H 2 O 2 : Hydrogen peroxide is the main oxidizing product of xanthine oxidase. Hydrogen peroxide is also directly produced by a number of oxidase enzymes, including glycolate and monoamine oxidases. Superoxide: In the biological system, superoxide ion is the most significant widespread ROS. It is formed as a result of various enzymatic auto oxidation reaction and non-enzymatic processes an electron is transferred to molecular oxygen. Copyright: © The Authors. This is an open access article under the terms of the Creative Commons Attribution NonCommercial ShareAlike 4. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. E-ISSN: Contact Home. |
ich beglückwünsche, die ausgezeichnete Antwort.
Ich entschuldige mich, aber meiner Meinung nach sind Sie nicht recht. Ich kann die Position verteidigen. Schreiben Sie mir in PM, wir werden reden.
Ich entschuldige mich, aber meiner Meinung nach irren Sie sich. Schreiben Sie mir in PM.