Free Radicals

What Can Antioxidants Do

To date, numerous studies have shown that antioxidants may protect against the following Macular degeneration Scientists report that a daily mix of antioxidants may slow macular degeneration in people who already have the disease. The recommendations include extra E, C, beta-carotene, and zinc. You may also need to take extra copper, because the zinc can oftentimes interfere with absorption. Free radicals can be Although beta-carotene is still considered a powerful antioxidant, it is no longer recommended in supplemental form. Many years ago, a study found that smokers who took beta-carotene supplements showed an increased risk of lung cancer. However, these findings certainly do not mean that beta-carotene has lost any importance among the antioxidant world. It does mean that until we have further information, people should solely focus on getting beta-carotene from food sources rather than supplemental megadoses. Immunity Researchers theorize that antioxidants might help to...

Fight Back with Antioxidants

Unfortunately, harmful agents called free radicals are produced when we breathe and process oxygen. In fact, these destructive bad guys can also be produced as a result of pollution, stress, pesticides, asbestos, x-rays, preservatives, exhaust fumes, tobacco smoke, and injury. As discussed in a previous chapter, free radicals trek all over the body and actually destroy the cell's DNA a cancer-promoting activity. The good news is that we naturally protect ourselves by forming antioxidants, substances that help our body's defense system fight off free radicals and preserve healthy cells. Furthermore, we know that certain foods are rich in nutrients that act as powerful antioxidants and might intensify the body's ability to degrade free radicals into harmless waste products that get eliminated before they do any damage.

Oxidative Stress and the Use of Antioxidants for Idiopathic OATs

Abstract Aim To examine the effects of ROS and OS on male fertility and to evaluate the use of antioxidants as a means of treatment to improve fertilization rates in subfertile males suffering from idiopathic oligoasthenoteratozoospermia (iOAT). Results Current research notes ROS-associated male factor infertility to be the most common potential etiology of impaired sperm quality. The various effects of these oxidants may be neutralized by antioxidants. Although antioxidant therapy has shown to potentially treat iOAT by improving semen parameters, its success remains limited. Our review calls for a deeper look and understanding of the type(s), dosage, and duration of antioxidant treatment used in order to apply its use in a clinical setting. Keywords Male infertility Oxidative stress Antioxidant treatment Idiopathic oligoasthenoteratozoospermia Antioxidants Anti-inflammatory drugs

Oral Antioxidant Therapy

As outlined in Chap. 23, many studies have been conducted examining the effect of a wide variety of different antioxidant combinations on sperm function and pregnancy outcome. Table 16.2 summarises the outcomes of the various antioxidant treatment regimes tested in a placebo controlled setting. In January 2011, the Cochrane collaboration, widely perceived as the definitive authority on evidence-based medicine, published a review on the effect of oral antioxidant therapy on sperm quality and pregnancy outcomes 178 . This review identified 34 randomised placebo controlled studies examining the effect of antioxidants on sperm quality and pregnancy outcomes in couples seeking fertility assistance. While 15 trials examined the effect of antioxidants on pregnancy rates, unfortunately only 3 studies examined live birth rate, the most meaningful clinical outcome. Further compounding the effective performance of a meta-analysis was the fact that dozens of different antioxidant combinations for...

Experimental Testicular Torsion and Antioxidant Therapy

Under normal condition, free radicals are produced and their effects are counterbalanced by the endogenous antioxidant system. When ROS generation exceeds the defense mechanisms' capacity to control, oxidative stress is occurred and contributes to reversible or irreversible cell damage 7, 140 . All living aerobic cells are normally exposed to some ROS, but if ROS levels rise, oxidative stress may occur, which results in oxygen and oxygen-derived oxidants, and in turn increases the rates of cellular damage. Oxidative stress has been shown to be a major cause of male infertility a large proportion of infertile men have elevated levels of seminal ROS 141 . ROS can directly damage spermatozoa by inducing peroxidation of the lipid-containing sperm plasma membrane, which decreases its integrity, and may also affect sperm motility by damaging the axonemal structure 142-144 . There are two available antioxidant strategies. In the first strategy, the superoxide radical and hydrogen peroxide...

Mitochondrial Antioxidants and Fertility

The deleterious effects resulting from the formation of ROS in the mitochondrion are, to a large extent, prevented by various antioxidant systems, and as such, mammalian mitochondria possess a relative abundance of enzymatic and nonenzymatic antioxidants designed to manage and counteract the ROS generated. An in-depth Phospholipid hydroperoxide GPx (GPx4) has broad selectivity, which allows it to reduce phospholipid hydroperoxides, H2O2, and cholesterol peroxides 68 . Three forms of GPx4 exist nuclear, short, and the long form found exclusively in the mitochondria. The long form RNA transcript is predominately expressed in testis in mice 69 . Localized to the sperm midpiece, mitochondrial GPx4 has been hypothesized to play a role as a structural protein rather than an enzymatic antioxidant since it has been shown to have completely lost its solubility and its scavenging enzymatic properties 70 . Two independent knockout models have also confirmed that when mGPx4 is not expressed, it...

Commercial Antioxidants

Several beverages, such as pomegranate juice, red wine, blueberry juice, cranberry juice, orange juice, and green tea, have been touted to have roles in improving erectile function in disease states via their ROS scavenging capacities. In animal models of arteriogenic ED, pomegranate juice decreased oxidative stress and improved, although it did not normalize, erectile function 171, 172 . This beneficial effect of pomegranate juice may be due to its main active ingredients such as polyphenol antioxidants. The other natural polyphenol, resveratrol, found mostly in grapes and red wine, restores penile function in animal models of hypercholesterolemia 173 - and diabetes 174 -induced ED. Cardiovascular protective effects of resvera-trol have been attributed to activation of eNOS and the improvement of endothelial function 175 . However, the exact role and mechanism of action of these commercial antioxidants on oxidative stress in the penis and erectile function await further basic science...

Day in the Life of an Antioxidant

We've all heard the news Antioxidants reduce your risk for heart disease and certain cancers and boost your immune system. So what exactly are antioxidants and how do they work As you know, every cell in your body needs oxygen to function normally. Unfortunately, the utilization of this oxygen produces harmful by-products called free radicals. Free radicals are also created from environmental pollution, certain industrial chemicals, and smoking. Outside the body, the process of oxidation is responsible for a sliced apple turning brown and the rusting of metal. Inside the body, oxidation contributes to heart disease, cancer, cataracts, aging, and a slew of other degenerative diseases. In other words, free radicals are the enemy. So why isn't everyone falling apart Your cells have their own special defense technique to fight off these radical monsters. What's more, scientists have unfolded compelling evidence suggesting that certain vitamins (specifically C, E, and beta-carotene) can...

Antioxidants A Practical Approach for Treating iOAT

As a multifactor disorder, iOAT presents a clinical challenge in the diagnosis and medical treatment of infertile men. ICSI has enabled iOAT to be circumvented mechanically however, it fails to address the fundamental factors contributing to male factor infertility. Oral supplementation of hormones and antioxidants has been the primary area of focus for pharmacotherapy treatment of iOAT. Significant improvements in sperm concentration, motility, and morphology have been reported 45 . Therefore, if it were possible to achieve a particular regimen of antioxidant(s) with the proper dosage and duration of intervention necessary to fully repair each aspect of the disorder, these men would have a greater probability of gaining normal sperm function. In order to consider a drug as active, it must improve sperm parameters and pregnancy rates in at least one blind, prospective, placebo-controlled trial, as well as additional trials from independent groups 46 . The aim of the following sections...

The Influence ofROS and Total Antioxidant Capacity in IVF and ICSI Cycles

In more recent study, Aurrekoetxea et al. describe, for the first time, serum oxi-dizability and antioxidant status in women undergoing an IVF cycle. The author found that the serum is less protected from oxidation after the cycle, showing a lower resistance to in vitro oxidation, reduced total antioxidant activity (TAA), and decreased levels of hydrophilic antioxidants and vitamin E. These results strongly suggest increased ROS production and the presence of oxidative stress 212 .

What Are Free Radicals

Free radicals are a group of atoms or molecules that are highly reactive due to having one or more unpaired electrons 7 . As a result of having an incomplete outer valance shell, these molecules attempt to react with other molecules in their vicinity in order to gain one or more electrons. However, once a molecule loses an electron to a free radical, a chain reaction is created, as now the former molecule becomes a free radical itself (Fig. 13.1). The chain reaction created from free radicals can have catastrophic effects for living cells. ROS are a collection of radicals and nonradical derivatives of oxygen. Free radicals derived from nitrogen are called reactive nitrogen species (Table 13.1). The most common ROS that is produced by spermatozoa is the superoxide anion radical this in turn forms hydrogen peroxide (strong oxidizer) on its own or by the action of superoxide dismutase 8 . Plasma membrane of the spermatozoa is rich in polyunsaturated fatty acids (PUFA). Because their...

In Vivo and In Vitro Antioxidant Treatments

Oral antioxidant supplements may be used to counteract OS and treat male infertility. Studies have shown that antioxidants correlate with improvement in sperm parameters however, in excess, these oral antioxidant supplements may have detrimental effects 83 . As an example, improvement in sperm motility and lower levels of ROS were attributed to vitamin E and selenium oral supplementation 84 . Other antioxidant supplementations that have been proven to be effective in reducing ROS levels include glutathione, l-carnitine, vitamin A, and -acetyl cysteine 39, 50 . Antioxidant treatments can be also added to culture media in vitro during sperm preparation techniques in order to improve in vitro sperm fertilization ability. Vitamin C supplementation alone and in conjunction with vitamin E has been shown to be effective both orally and in culture media 85, 86 . Media supplementation with vitamin C and urate can lead to protection of spermatozoa from DNA damage 87 .

Determination of the Seminal Antioxidant Capacity

The antioxidant activity in biological fluids can be measured either by determination of the concentrations of the individual antioxidants or by the TAC 168, 169 . Among the different methodologies, which include the determination of the oxygen radical absorbance capacity 170 , ferric reducing ability 171 or the phycoerythrin fluorescence-based assay 172 . an enhanced chemiluminescent assay described by Whitehead et al. 173 is most commonly used. The principle of this assay is that the chemiluminescence emitted by a chemiluminescent substance such as luminol is inhibited by the antioxidant activity and then compared and standardized with that of Trolox acid), a water-soluble vitamin E analogue, and measured as molar Trolox equivalent. More recently, a reliable, accurate, more rapid and simple colorimetric method has been developed 174 ,

Chemiluminescence and the Antioxidant Properties of Seminal Plasma

Another variant on the chemiluminescence theme is to use this technology to monitor both ROS generation by the ejaculate and the antioxidant potential of the seminal plasma, with a view to generating a readout reflecting the balance between these two opposing forces. There can be no doubt that seminal plasma is a very powerful anti-oxidant medium that serves to protect spermatozoa during their perilous journey from the male to the female reproductive tract. This fluid is rich in antioxidant enzymes such as SOD, glutathione peroxidase, and some catalase as well as small molecular mass scavengers, including ascorbate, pyruvate, urate, alpha tocopherol, glutathione, albumin, beta carotene, hypotaurine, and ubiquinol 10, 60, 61 . The ability of this fluid to protect spermatozoa from the emission of free radicals by contaminating leukocytes has been clearly demonstrated, as have the adverse consequences of removing this antioxidant protection when leukocytes are present in the sperm...

Antioxidants in the Semen

In view of the male germ cell's high vulnerability to extrinsic and intrinsic ROS as well as lack of its own protection, spermatozoa have to receive protection against oxidative stress through relevant scavengers by the male and or female reproductive tracts. Therefore, in the male, the testis and the accessory sex glands that are producing the seminal plasma have to provide substances and mechanisms for such protection. Indeed, seminal plasma is the biological fluid containing highest concentrations of antioxidant substances, even more than in any other physiological fluid. Basically, this antioxidative protection can be separated into two systems, interceptive and preventive. Among the scavenging antioxidants another distinction between enzymatic and non-enzymatic systems can be made 133 .

Endogenous Antioxidants in the Penis in ED

Endothelial and smooth muscle cells of the rat penis contain antioxidants such as SOD3 37,46,113,114 , catalase 115 , reduced glutathione 38, 65 , and glutathione peroxidase 116 . Cavernosal tissue and blood from men contain vitamin C, albumin, bilirubin, uric acid, and glutathione 42, 117 . Controversial data were, however, obtained regarding the status of endogenous antioxidants in the diseased penis. Penis from aged animals exhibit decreased levels of reduced glutathione but increased cytoplasmic SOD expression 38 . although extracellular SOD protein and RNA expressions and SOD activity remain unchanged 37 . The diabetic penis exhibits decreased mRNA expression for catalase 118 , while glutathione levels were reportedly decreased 47 or increased 42 . Similarly, while mRNA expression of SOD2 is decreased in the diabetic rat penis 118 , SOD activity remains unchanged 46 . The corpus cavernosum of hypertensive rats exhibits decreased SOD activity 68-70 . while corpus cavernosal tissue...

Oxidative stress and antioxidants

Oxygen is essential for human life and necessary for energy production, but in some forms it can be damaging to the body as reactive oxygen species (ROS) free radicals. The majority of ROS are produced in the mitochondrial electron transport chain during energy production. Physical exercise augments the production of free radicals and other forms of reactive oxygen species. End-products of oxidative damage are observed in the blood and tissues after acute intensive exercise as well as signs of decreased levels of antioxi-dants in some studies. Strenuous exercise may manifest an imbalance between the production of ROS and antioxidant defences, resulting in an oxidative stress situation in the body 86 . In fact there is some evidence which implicates ROS as an underlying cause of exercise-induced muscle fatigue and damage. During an acute bout of strenuous exercise the immune system is activated and produces a substantial amount of ROS, which may cause an inflammatory process. The...

Extracellular Antioxidants Protect Against Lipid Peroxidation

In order to prevent intracellular oxygen radical-induced damage, spermatozoa mostly rely on superoxide dismutase (SOD) and glutathione peroxidase (GPX) as the primary antioxidant enzymes, since mammalian spermatozoa have been shown to lack catalase activity. Spermatozoa are largely bereft of cytoplasm and cytoplasmic space, and therefore, these enzymes must exert their antioxidant activity while bound to the cytoskeleton of the axoneme, as it has been suggested for glycolytic enzymes 26 , The role of intracellular GPX and SOD in preventing lipid peroxidation and motility loss has been previously reported 4, 27 . Inhibition of intracellular SOD results in the release of very high levels of superoxide anion to the extracellular medium thus providing support for the important role of SOD in preventing intracellular oxygen radical-induced damage. On the other hand, in order to prevent extracellular oxygen radical-induced damage, these cells rely heavily, but not exclusively, on the...

Antioxidants

Antioxidants are substances that are able to protect organisms from oxidative stress. A distinction is drawn between three types of antioxidants enzymatic antioxidants, nonenzymatic antioxidants, and repair enzymes. Well-known naturally occurring antioxidants are vitamin C (ascorbic acid), which are contained in many citrus fruits, or on the other hand members of vitamin E family, which appear for example in nuts and sunflower seeds. Also b -carotene and lycopine, which also belong to the family of caro-tenoides, are further examples of natural antioxidants. On the other hand, there are many synthetic

Seminal Antioxidants

Depending on the solubility in water or in lipids, antioxidants can be classified into two main divisions hydrophilic which are water-soluble or hydrophobic which are lipid-soluble. In general, water-soluble antioxidants react with oxidants in the cell cytosol and the blood plasma, while lipid-soluble antioxidants protect cell membranes from lipid peroxidation. These compounds can be formed in the body or obtained from the diet 26 . The different types of antioxidants are present at various concentrations in body fluids and tissues, with some such as glutathione or ubiquinone mostly present within cells, while others such as uric acid being more evenly distributed. Some compounds contribute to antioxidant defense by chelating transition metals and preventing them from catalyzing the production of free radicals in the cell. Particularly important is the ability to sequester iron, which is the function of iron-binding proteins such as transferrin and ferritin. Selenium and zinc are...

Free Radicals

Free radicals are reactive chemical elements that carry one or more unpaired electrons 11, 12 . These electrons induce oxidation to other cellular structures as they bind with them, of these structures nucleic acids, proteins and lipids of the cell membranes 13 . They are required by the cells as intracellular signaling necessary for many cell functions such as cell proliferation, differentiation, and migration 14, 15 . Also in reproductive system, they are important for various reproductive functions 16 , However, high levels of free radicals may alter spermiogenesis resulting in production of abnormal spermatozoa 12 .

Antioxidant Therapy

In addition, bladder outlet obstruction due to BPH induces cyclical ischemia rep-erfusion at the bladder wall, leading to perturbation of intracellular Ca2+ homeostasis and subsequent activation of a variety of Ca2+-regulated enzymes and the generation of ROS such as O2- and OH 165 . The ROS-mediated oxidation of biomolecules probably causes partial denervation of the detrusor muscle with the subsequent development of supersensitivity, leading to bladder instability 166 . Therefore, ROS may be one of pathogenic factors in the inflammation of the dysfunctional detrusor and enlarged prostate, so that antioxidants may be useful in the treatment of BPH. The treatment goals for BPH are to relieve the irritable and obstructive symptoms. Options for treatment include surgical therapy and pharmaceutical intervention Antioxidant compounds that scavenge oxidative stress may be useful in helping to overwhelm its mutagenic effects 170 . Dietary components supplements that have antioxidant...

Lessons from the Aptamers Ribozymes Deoxyribozymes Generated by In Vitro Selection

In light of all the successes one might ask if there is anything that RNA cannot do. Given the challenge of keeping free radicals localized so they do not cause harm, chemical mechanisms that involve radicals may be difficult for RNA (Joyce, 2002). However, as with naturally occurring proteins, oligonucleotides can use cofactors to introduce structural or chemical characteristics they do not possess (for example, Roth and Breaker, 1998 Tsukiji et al., 2004). With the right cofactor, perhaps B12 or a quinone, a ribozyme or deoxyribozyme may be able to catalyze a radical-dependent reaction such as ribonucleotide reduction (Stubbe, 2000).

Intrinsic Causes of Mitochondrial ROS Generation

Mature human spermatozoa have been recognized to exhibit many but not all features of apoptotic signal transduction pathways including the externalization of phosphatidylserine (PS) (annexin-V binding), activation of caspases 1, 3, 8, and 9 96-98 , mitochondrial dysfunction, and ROS generation 99-101 . One pathology that has been associated with apoptosis in spermatozoa is varicocele. Spermatozoa from men with this condition show higher levels of externalization of PS mitochondrial dysfunction and nuclear DNA damage 102 . In vitro exposure of human spermatozoa to oxidative stress mediator H2O2 can trigger the activation of caspases and externalization of PS 103 . In contrast, addition of antioxidants (catalase) to spermatozoa prior to H2 O2 will prevent this apoptotic response 104 . Activation of the apoptotic cascade by PI3 kinase inhibitor, wort-mannin, has also shown to result in increased mitochondrial ROS generation, caspase activation, and PS externalization 99 ,

Environmental and External Factors Related to Mitochondrial ROS

In smokers, the overall mitochondrial ETC function is significantly decreased which also correlates with increased peroxidative damage to lymphocyte membranes 126 . An extremely large Danish study of 2,542 healthy men, without bias towards reproductive history, discovered that compared with nonsmokers, smokers exhibited significantly decreased sperm concentration, semen volume, motility, and total sperm count 127 . Although the changes observed were only minor (20-30 decrease), such effects may further compound an already-existing minor reproductive condition or combine with other xenobiotics to further reduce fertility. Overall, the smokers presented in the study exhibited increased seminal ROS production and decreased antioxidant levels. A number of independent studies have also shown that smoking results in higher levels of DNA damage in the human spermatozoa in comparison to nonsmokers 124, 128, 129 . Also, a higher rate of smoking observed in men is associated with corresponding...

Shikimic Acid Derivatives

Shikimic acid (4) is a key synthetic intermediate for plants since it is the key precursor for both the flavonoids and lignin (Bu'Lock, 1965 Mann et al., 1994). The flavonoids are important to plants as antioxidants, colors, protective agents against ultraviolet light, and the like, and lignin is a key component of the structural materials of plants, especially woody tissues. Shikimic acid is synthesized from phosphoenol pyruvate (1) and erythrose-4 phosphate (28), as shown in Figure 5.7, and thus its biosynthesis starts from the carbohydrate pathway. Its derivatives can usually be recognized by the characteristic shikimate pattern of a six-membered ring with either a one- or three-carbon substituent on position 1 and oxygenation in the third, and or fourth, and or fifth positions. However, the oxygen atoms of the final products are not those of the starting shikimate since these are lost initially and then replaced.

Note about Some Especially Popular Vitamin Supplements

Vitamin E, a fat soluble vitamin, is essential for the formation, growth, and repair of bones and for normal calcium absorption and immune function. It is obtained mainly through exposure to sunlight, but it also can be obtained from foods such as green leafy vegetables, nuts and seeds, and some oils. Evidence does not support the use of vitamin E supplements to prevent cancer. Further, because it acts as an antioxidant and can interfere with some chemo drugs, cancer patients should avoid taking vitamin E supplements during treatment. Research also shows that more than 400 International Units (IUs) a day may increase the risk of stroke and the risk of death.

General Considerations

There has been an increasing interest throughout the world in the use of natural ingredients for health, especially tea. Tea is the world's second most popular beverage after water. Green tea accounts for approximately 20 of all tea consumed. It has been claimed that overall health of the body, especially the oral cavity, can be maintained by the consumption of green tea. Green tea is not fermented therefore, it contains polyphenols that are inactivated in the fermentation process of black tea production. Green tea has been consumed in East Asia, where its benefits have been claimed for centuries. Green tea polyphenols possess antioxidant and antiviral properties that account for its benefits these benefits have been touted to include lowering blood pressure, lowering cholesterol, stabilizing blood glucose, inhibiting bacterial growth, and blocking many carcinogenic agents. Polyphenols have been shown to inhibit the growth of Streptococcus mutans, the major etiologic bacterium...

Research Evidence to Date

As of the late 1990s, antioxidants vitamins C, E, and beta carotene, which the body converts to vitamin A, starred as some of the most popular supplements. They were thought to provide protection against heart disease and cancer, and were widely available at health-food stores and pharmacies. The antioxidant story is a good example of why large and thorough studies are necessary before we really know if something works. Antioxidant supplements became popular because studies showed less cancer and heart disease among people who ate more fruit and beta carotene-rich vegetables (dark leafy green, yellow, and orange vegetables) than among people who consumed fewer vegetables and fruits. That is still accurate, but antioxidant supplements turned out to be no substitute for the foods themselves. Three major studies, involving a total of 74,000 men and women, showed definitively that beta carotene supplements do not lower the risk of cancer or heart disease.

Fibromyalgia Tired of Being Sick and Tired

Acupuncture, massage, and Chinese herbal medicine are recommended as effective treatments by the Fibromyalgia Network (see Appendix D, State and National Organizations )- The Network is an organization that provides information to patients with this potentially debilitating condition. Moxi-bustion or infrared heat treatments are also useful in driving out the cold. Nutritional supplements such as antioxidants (coenzyme Q10, vitamins E and C) are helpful in managing this condition, as are dietary changes to eliminate dampness and build immunity.

The Negative Impact of Unsaturated Fatty Acids and Lipid Peroxidation

The association between male infertility and the peroxidation of polyunsaturated fatty acids (PUFA) has been appreciated since the landmark studies of Thaddeus Mann and colleagues at the University of Cambridge. Mann et al. drew attention to the vulnerability of human spermatozoa to lipoperoxidative damage because of their particularly high PUFA content 23 . They also demonstrated that when washed human spermatozoa were treated with as little as 30 nmol of lipid peroxide mL, they become irreversibly immotile within a few minutes. In addition, this seminal paper 23 highlighted the significance of seminal plasma antioxidants in protecting spermatozoa from oxidative damage.

Kinetics Of Chain Polymerisation

Initiation occurs as a molecule of intiator decomposes to free radicals (Reaction 2.9), where kA is the rate constant for the reaction. These newly generated free radicals can then interact with monomer molecules preserving the free radical centre (Reaction 2.10). These two processes may be considered to form part of the initiation stage, the first of them being rate determining. Early on in the overall polymerisation the rates of initiation and termination become equal, resulting in a steady-state concentration of free radicals. Here R, R,. From this the two equations can be combined to solve for M-

Initial Symptoms and Signs

Brain tumors produce clinical change either through regional parenchymal or diffuse intracranial effects. Regional parenchymal effects of brain tumors include compression, invasion, and destruction of surrounding brain. Hypoxia, arterial or venous competition for nutrients, altered transmitter metabolism and electrolyte concentration, and the spread of cytokines and free radicals alter the cellular environment, disrupting normal neural and glial cell function. Irritation (e.g., focal seizures) or depression (e.g., neurologic deficits) of neuronal function can be the

Free Radical Scavenging Assay

This spectrophotometric assay uses the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) as a reagent (Yadegarinia et al., 2006). The model of scavenging stable DPPH-free radicals can be used to evaluate the antioxidative activities in a relatively short time (Conforti et al., 2006). The samples are able to reduce the stable free DPPH radical to 1,1-diphenyl-2-picrylhydrazyl that is yellow colored. The hydrogen or electron donation abilities of the samples are measured by means of the decrease of the absorbance resulting in a color change from purple to yellow (Gutierrez et al., 2006). Another procedure can be applied for an EO. A dilution of the EO in toluene is applied onto a thin-layer chromatography (TLC) plate and toluene-ethyl-acetate is used as a developer (Sokmen et al., 2004a). The plates are sprayed with 0.4 mM DPPH in methanol. The active compounds were detected as yellow spots on a purple background. Only those compounds, which changed the color within 30 min, are...

PCarotene Bleaching Test

The lipid peroxidation inhibitory activities of EOs are assessed by the b-carotene bleaching tests (Yadegarinia et al., 2006). In this method, the ability to minimize the coupled oxidation of b -carotene and linoleic acid is measured with a photospectrometer. The reaction with radicals shows a change in this orange color. The b-carotene bleaching test shows better results than the DPPH assay because it is more specialized in lipophilic compounds. The test is important in the food industry because the test medium is an emulsion, which is near to the situation in food, therefore allowable alternatives to synthetic antioxidants can be found. An only qualitative assertion uses the TLC procedure. A sample of the EOs is applied onto a TLC plate and is sprayed with b-carotene and linoleic acid. Afterwards, the plate is abandoned to the daylight for 45 min. Zones with constant yellow colors show an antioxidative activity of the component (Guerrini et al., 2006).

Xanthine Xanthine Oxidase Assay

Superoxide radicals are produced by a xanthine-xanthine oxidase system. Xanthine is able to generate O2 and H2O2 by using xanthine oxidase as a substrate. The superoxide radicals are able to reduce the yellow colored nitro triazolium blue (NTB) to the blue formazan, which is used for monitoring the reaction. The superoxide anions are measured spectrophotometrically. This test method was developed to explore the reaction between antioxidants and O2 So the inhibition of the superoxide reductase is a mark for the ability of antioxidative activity.

The DRIs Dietary Reference Intakes

Because scientific knowledge regarding diet and health has increased, the Food and Nutrition Board has recently expanded its framework and developed the Dietary Reference Intakes (DRIs) for several vital nutrients. It is forecasted that over the next three to four years additional groups of nutrients including phtyoestrogens, antioxidants and phytochemicals will also be slated for review toward DRI development. These new DRI standards include the RDAs as goals for intakes, plus three new reference values the estimated average requirement (EAR), the tolerable upper limit (UL), and the adequate intake (AI). On the two reference charts provided here, you'll notice that some nutrients are listed as DRIs, some as RDAs, an some as AIs a bit confusing but all you'll need to understand is the actual recommended amount.

Watersoluble vitamins Vitamin B complex

Vitamin C is not technically a vitamin for healthy dogs and cats because all that is required can be synthesized by the animal. Vitamin C mainly functions in the body as an antioxidant and free radical scavenger and is needed for the synthesis of collagen. It was postulated that huge doses of vitamin C could be beneficial in preventing hip dysplasia but this has not been proved. Recent research has focused on the use of supplemental vitamin C in the prevention of some types of cancer.

Fatsoluble vitamins Vitamin A

Vitamin E is an important antioxidant and the requirement for vitamin E increases with the dietary levels of polyunsatu-rated fatty acids (PUFA). Vitamin E is only synthesized by plants and the richest natural sources are vegetable oils, seeds and cereal grains. The clinical manifestations of vitamin E deficiency vary markedly between species. In dogs the main clinical signs are degenerative skeletal disease with muscular weakness and gestational failure. In cats deficiency can arise when diets that are high in PUFA, such as oily fish, are fed. The clinical signs associated with vitamin E toxicity in cats include the occurrence of painful subcutaneous nodules, termed steatitis, as well as myocarditis and myositis.

Acidosis and Hyperglycaemia

Injury.19 While the general consensus is that preischaemic hyperglycaemia is deleterious, in some studies it has been shown to delay the onset of ischaemic Ca++ influx from the ECF and potentiate reextrusion of Ca++ following recirculation. These findings may reflect the modulatory effects of the type of ischaemia (focal versus global), its duration and extent and the completeness of the ischaemic insult.1020 It is thought that acidosis enhances production of reactive free radicals, causes oedema, aggravated tissue damage and delayed seizures and prevents recovery of mitochondrial metabolism.1419 However, it still remains to be fully established whether exaggerated intra-ischaemic acidosis enhances postischaemic production of reactive oxygen species (ROS).

Lipid Peroxidation and Free Radical Formation

Free radicals are reactive chemical species that damage DNA, denature structural and functional proteins and result in peroxidation of membrane lipids. Free radicals are formed as a consequence of several processes including phospholipase activation by cytosolic Ca++, transitional metal reactions which involve free iron, arachidonate metabolism and oxidant production by inflammatory cells. These processes result in the formation of superoxide radicals, which are protonated in the ischaemic environment of the ischaemic brain to produce highly reactive hydroxyl radicals. Normally aerobic cells produce free radicals, which are then consumed by free radical scavengers, e.g. a-tocopherol and ascorbic acid, or appropriate enzymes, e.g. superoxide dismutase. In states where enzymatic processes are disrupted (ischaemia) or hyperoxia occurs (reperfusion), there may be excessive production of oxidants, in particular superoxide, hydrogen peroxide and the hydroxyl radical. These highly reactive...

Relationship of Cytokines with Redox Status of Semen

Some cytokines act as regulators of the physiological levels of ROI in the seminal plasma 57, 111 . Some authors have suggested that particular cytokines modulate the expression of genes responsible for the redox system in the semen 56, 104 , Among all the cytokines, the production of chemotactic, proinflammatory cytokine IL-8 appears to be a specific response to oxidative stress. DeForge et al. 112 have demonstrated that oxidative stress is an important regulator of IL-8 gene expression in human epithelial cells and fibroblasts. Moreover, a unifying mechanism underlying this topic may involve regulation of NF-kB by the redox status of the cell, namely, its activation by ROI and its inhibition by various antioxidants in cells stimulated with cytokines or other agents like LPS or PMA 113, 114 . An increase in ROI production by human sperm was observed after the addition of IL-1a, IL-1b, or TNF-a, the result of which was an increase in sperm membrane lipid peroxidation, as measured by...

Epidemiology And Etiology

Flammatory cytokines, immune system disorders, trophic factor deficiency, signalmediated apoptosis, and environmental toxins. Conditions that may promote oxidative stress include increased monoamine oxidase-B metabolism or decreased glutathione clearance of free radicals which can promote cell dysfunction and death. Drugs that deplete central dopamine, such as some antipsychotics, amoxapine, antinausea drugs (e.g., prochlorperazine), and metoclopramide, worsen PD symptoms.1-4

Differences Between Tissue Hypoxia And Current Model

Logical alterations such as acid tissue pH, generation of both free radicals and reactive oxygen species, induction of inflammatory cytokines and chemokines, and, in the case of tumors, breaching of the integrity and replacement of portions of the vessel wall by malignant cells (Brown and Giaccia 1998 Carmeliet and Jain 2000 Coussens and Werb 2002). Moreover, additional transcription factors are up-regulated by hypoxia independent of HIF-1a or HIF-2a including Egr-1 (Yan et al. 2000), NFkB (Royds et al. 1998), Jun amino-terminal kinase (Jin et al. 2000), c-Jun (Alfranca et al. 2002), c-fos (Premkumar et al. 2000), p53 (Koumenis et al. 2001), and ATM (Hammond et al. 2002). These disparate elements likely conspire to produce a leaky hypoxic vasculature. Further studies will be needed to determine whether induction of HIF-1a itself or a selected set of HIF-target genes can produce an increase in a functional vasculature to minimize damage and to accelerate function restoration in...

Radiation and plasma surface treatments

Ultraviolet (UV) radiation treatment of polymer surfaces is another interesting emerging technology, since research with this process has recently examined its advantages in textile treatments of polymer films and membranes. Graft copolymerisation is one of the techniques used for polymer surface functional modification and is described by Cook and Smith (2003). Basically, the process involves extraction of hydrogen atoms by using UV radiation in combination with a photo initiator to generate free radicals. Monomers can then combine with the free radicals to form grafted polymer chains. The integrity of the base polymer is unaffected by the process and the grafts are chemically fixed.

Clinical Features

For all histologic entities covered in this chapter, magnetic resonance imaging (MRI) is the standard and most helpful neu-roradiologic method because lesions containing melanin have unusual paramagnetic properties on both T1- and T2-weighted scans. On T1-weighted MRI scans, the melanin pigment within the melanocytes appears hyperintense to white matter and appears isodense to gray matter. On T2-weighted scans, the melanin-containing lesions appear hypointense compared with both white and gray matter. After infusion of intravenous contrast agents, melanocytic lesions diffusely enhance with intensity corresponding to the level of melanin pigment contained within the lesion. Paramagnetic free radicals associated with melanin are thought to be responsible for its unique MR prop-erties.24 Although methemoglobin and fat have similar MR signal properties as melanin, enhancement on postcontrast MR images can help distinguish melanocytic lesions from other lesions.24 On computed tomography...

Importance of Oxidative Stress and ROS in Male Infertility

Sperm dysfunction is one of the leading causes of infertility. Despite much research, there is limited knowledge about the causes of sperm dysfunction. However, oxidative stress (OS) has been identified as one of the causes of abnormal sperm function. OS refers to the state in which free radicals overwhelm the body's antioxidant capacity 21 an excess of ROS can have harmful effects on the tissues and organs 9, 10 . ROS has been shown to negatively affect sperm quality and function 22, 23 . For normal male fertility, a fine balance between the generation of ROS and its removal is very important. Excess of ROS also has a negative impact on the pregnancy outcome as well as the assisted reproductive techniques 24, 25 . Moreover, excess ROS can damage DNA in spermatozoa, induce cell apoptosis, and cause lipid peroxidation, which leads to morphological abnormalities, decrease in fertility, and increased sperm membrane permeability 26-28 . It is important to effectively detect the amount of...

Calcium Channel Blockers

Calcium antagonists are often used as renovascular vasodilators in selected situations, e.g. renal transplantation. In kidney recipients, diltiazem has been shown to cause vasodilatation within the kidneys and improve intrarenal circulation. They also decrease calcium influx and production of oxygen free radicals on reperfusion after the ischaemic insult. In these patients, calcium antagonists significantly improve renal function and decrease the incidence of post-transplant acute tubular necrosis. Furthermore, they may reduce the vasoconstrictive action of cyclosporin. In spite of all the apparent beneficial effects, calcium antagonists have failed to improve graft survival.

Impact of Varicoceles

Due to the release of nitric oxide synthase and xanthin oxidase significantly higher levels of oxidative stress were detected in the spermatic vein 122-124 . Additionally, Mostafa et al. 125 found that, apart from increased levels of oxidative stress as determined by means of the seminal concentrations of MDA, hydrogen peroxide and nitric oxide, levels of antioxidants (SOD, catalase, GPx, vitamin C) were significantly reduced in spermatic venous blood as compared to peripheral blood. This finding is consistent with the observation by Shamsi and Dada (2010 personal communication) that seminal concentrations of MDA and antioxidants significantly and It is also not surprising that the seminal concentrations of ROS and total antioxidant capacity (TAC) were increased and decreased, respectively 126 . Consequently, vari-cocele not only does affect spermatogenesis leading to poor sperm count, morphology and DNA integrity 127 but also leads to deteriorated sperm functionality by seminal...

Highpressure Liquid Chromatography

To provide adequate information for unequivocal identification. HPLC is particularly suitable in the separation of high-molecular-weight (up to 6 million) substances and thermally unstable biologically active products that cannot be volatilized without decomposition aqueous and nonaqueous samples can be analyzed. HPLC has been applied to the analysis of natural and synthetic products such as amino acids, antibiotics, antioxidants, flavonoids, carotenoids, lipids, flavoring and aroma compounds, herbicides, pesticides, hormones, steroids, mycotoxins, pol-yaromatics, proteins, sugars, purines, dyes, vitamins, and water and air polutants. An example of HPLC applications includes the detection of the highly toxic aflatoxins sometimes found in peanuts, wheat, corn, and other grain crops. They are produced by fungus on the grain and are considered to be dangerous to human health when their concentration exceeds 20 ppb.

Interfacing Supercritical Fluid Chromatography with Fourier Transform Ir Sfcftir

SFC-FTIR is a very useful technique in characterizing chemical additives in polymers. Many of these additives, which include slip agents, plasticizers, UV absorbers, light stabilizers and antioxidants are thermally labile or have a high molecular mass which makes them difficult to analyze by other methods.

Oxidative Stress and Testicular Torsion

Abstract Testicular torsion is a medical urologic syndrome that constitutes a surgical emergency affecting newborns, children, and adolescent boys. The main pathophysiological event in testicular torsion is ischemia (torsion) followed by reperfusion (detorsion) of the testis, and multifactorial mechanisms seem to mediate this condition. Testicular damage after ischemia reperfusion (I R) is related to the duration of ischemia and to the severity of the torsion. I R injury is associated with activation of neutrophils, inflammatory cytokines, and adhesion molecules with increased thrombogenicity, release of massive intracellular calcium, and overgeneration of reactive oxygen species and reactive nitrogen species. Although the results are not conclusive and the molecular mechanism by which antioxidants control male fertility have not yet been clearly identified, several antioxidant enzymes and antioxidant drugs have been studied to prevent such I R injury in testis. Antioxidant therapy...

Varicocele and Oxidative Stress

Abstract A varicocele is an abnormal dilatation of the pampiniform plexus within the spermatic cord. It is the most common male infertility factor, with multiple potential etiologies involved in its development. However, despite ongoing extensive research on varicoceles, the exact mechanism(s) by which varicocele influences male fertility is not known. Recent studies have shown that infertile men with varicocele have higher levels of seminal oxidative stress (OS) markers, and or lower seminal antioxidant levels, than do fertile men and infertile men without varicocele. The abnormally high levels of seminal OS biomarkers (e.g., reactive oxygen species, malonaldehyde) in infertile men with varicocele is clinically relevant as these markers have been associated with poor sperm function and reduced fertility potential. In addition, infertile patients with varicocele possess high levels of sperm DNA damage and the mechanism of varicocele-induced sperm DNA damage is believed to be at least...

Nonenzymatic Oxidation of Drugs

The nonenzymatic autoxidation of catecholamines also plays an important role in the physiology and aging of the CNS. Dopamine, like most catecholamines, can be easily oxidized by molecular oxygen in physiological solutions (i.e., at neutral pH and in the presence of transition metal traces) (104). During autoxidation, both semiquinones and quinones are formed, and they react with molecular oxygen to produce reactive oxygen species. Numerous data suggest that the cytotoxicity of levodopa, a dopamine precursor used for long-term therapy of Parkinson's disease, is likely due to the action of free radicals formed as a result of its autoxidation (105, 106). Moreover, quinoid compounds derived from the autoxidation of endogenous catechols polymerize to form neuromelanin, which contributes to the vulnerability of dopaminergic neurons in Parkinson's disease (107). Finally, quinoids products can crosslink with neurofilament proteins (108) and with cysteine to form cytotoxic cysteinylcatechols...

Recreational Drugs and ROS Production in Mammalian Spermatozoa

Abstract Oxidative stress is caused by an imbalance between the production of reactive oxygen species (ROS) and antioxidant capacity of the cell. Oxidative stress appears to be the major cause of DNA damage in the male germ line. Furthermore, many studies have indicated a significant correlation between DNA damage and high levels of ROS in infertile patients. Male reproductive health is already under threat from a range of environmental factors including endocrine disruptors, toxic pollutants, ionizing and lifestyle factors such as sexually transmitted infections, alcoholism, smoking, and anabolic steroid use. Further hazards such as fast food, recreational drugs, and stress levels may also impair male fertility. Recreational drugs such as alcohol, barbiturates, amphetamines, THC, PCP, cocaine, and heroin, but also includes caffeine in coffee and cola beverages, and environmental factors may increase ROS production, leading to DNA damage and further male infertility.

Clinical Presentations 2021 Varicocele

Infertile patients with varicocele present with higher levels of ROS and lower levels of seminal antioxidants leading to increased OS 78 . Published data have shown that the grade of varicocele has an impact on the levels of seminal ROS, which were proven to decline following the surgical correction of varicocele 78 . The relationship between varicocele and OS is not fully understood however, some mechanisms have been proposed. Significant amount of nitric oxide (NO) production are released from the dilated pampiniform plexus of veins leading to OS 79 . Additionally, NO may also interact with superoxide anion resulting in the production peroxynitrate, which result in further sperm damage 80 .

Unexplained Infertility

Unexplained infertility is diagnosed whenever routine testing methods including semen analysis fail to identify a reason for delay in achieving pregnancy. Other testing methods such as assessment of ROS and DNA fragmentation may reveal the actual cause of infertility in these cases 82 . Higher seminal ROS levels and lower antioxidant levels were shown in men diagnosed with unexplained infertility compared to healthy controls 83 . Moreover, abnormal levels of ROS were seen in 25-40 of men diagnosed with unexplained infertility 84 .

Adaptive Effects Of Cytokines In The Heart

Ocardial cells are continually susceptible to oxygen-derived free radicals, TNF and IL-1 may play important roles in protecting the heart against oxidative stress, particularly during ischemia and reperfusion injury. TNF has also been shown recently to up-regulate the expression of heat shock protein 72 (HSP 72) (Nakano et al. 1996), a protein that is thought to protect the heart against ischemia reperfusion injury (Marber et al. 1995 Plumier et al. 1995). Finally, proinflammatory cytokines such as TNF and IL-1 p have been shown to activate the transcription factor nuclear factor-kappa B (NF-kB), which has been shown to be cytoprotective under certain circumstances, presumably through up-regulation of one or more cytoprotective genes, including MnSOD, the cellular inhibitors of apoptosis 1 and 2 (c-IAP1 and cIAP2), and the members of the Bcl-2 family, including Bcl-2, Bfl-1, and Bcl-xL (Stehlik et al. 1998 Wang et al. 1998 Erl et al. 1999 Lee et al. 1999 Narula et al. 1999).

Vitamins and Minerals

While there's nothing wrong with taking a daily multivitamin, megadoses aren't a good idea because their long-term safety remains in question. Over the years, various supplements have been recommended for an assortment of ailments. B-vitamins, for instance, were used to treat diabetic neuropathy, but their beneficial role was never proven and they're not recommended as a therapeutic option. Although chromium piccolinate was reported to have a good effect on blood-sugar control, it was never conclusively demonstrated. One antioxidant, alphalipoic acid, is a prescription drug in Germany that has been used to treat diabetic neuropathy. Although studies are underway in the United States, results will not be available for years.

Oxidative Stress and Spermatozoa Functions 2141 Association Between Oxidative Stress and Subfertility

Increased levels of ROS were correlated with female infertility as well as male subfertility 96 , Low levels of natural antioxidants production or excessive ROS The presence of high amounts of polyunsaturated fatty acids (PUFA) in the plasma membrane of spermatozoa make it susceptible to damage by oxidative stress 99 , ROS negatively affect sperm function by contributing to the occurrence of lipid peroxidation (LPO) 99, 100 , Furthermore, the severity of oxidative stress increases as the levels of antioxidants decreased 101, 102 . Hammadeh et al. 105 found in patients undergoing IVF or ICSI therapy that the concentration of ROS and total antioxidants (TAS) in seminal plasma did not significantly differ however, they showed a negative correlation between ROS concentration in seminal plasma and sperm vitality, membrane integrity, sperm density, chromatin condensation, and DNA single-stand breaks in both IVF and ICSI groups 105 .

Oxidative Stress and Embryo Development

Similarly, addition of antioxidants to the media used in ART improves the implantation and clinical pregnancy rates 45 . For example, addition of metal ion chelating agents like EDTA to the culture media may decrease the production of ROS and help in successful embryo development and pregnancy 45 .

Possible MCI Therapies

Vitamin E can ameliorate oxidative stress, and a primary event in AD pathology is believed to be oxidative stress involving the production of free radicals. Postmortem examinations of individuals with AD have revealed oxidative damage in neurofibrillary plaques and tangles as well as pyramidal neurons. Vitamin E is a lipid-soluble antioxi-dant that interacts with cell membranes, traps free radicals, and inhibits beta-amyloid-induced cell death. So far, trials have produced mixed results. One placebo-controlled study revealed benefits in treating moderately impaired AD patients with vitamin E (alpha-tocopherol) at 2000 IU day This yielded delays in functional decline, particularly in terms of the need for placement in long-term care facilities (Sano et al., 1997).

Role of Oxidative Stress in Polycystic Ovary Syndrome

Protein oxidation status often is assessed with a colorimetric assay that measures protein carbonyl (PC) content, after extracting the serum with dinitrophenylhydra-zine. Fenkci et al. 210 demonstrated that the PC level was significantly higher in PCOS patients with normal BMI compared with controls. This observation of higher protein oxidation suggested that free radicals damage proteins in PCOS patients 210 Furthermore, protein carbonyls were shown to have a positive correlation with fasting insulin, suggesting a strong association between insulin resistance and protein oxidation in PCOS.

Critical Commentary

Lycopene is one of the most potent, highly lipophilic antioxidants. Low lycopene intake has been associated with a decrease in sperm concentration, motility, and morphology levels 60 . While its main action is antioxidative, it also has antiproliferative, immunomodulatory, and anti-inflammatory effects and influences on cell differentiation, communication, and signaling. The receptor for advanced glycation end products (RAGE) is a cell surface multiligand receptor that is activated by advanced glycation end products (AGEs). Activation of RAGE induces cellular response and results in OS 62 . Since OS is recognized as an important contributing factor to male infertility 63 , the release of sRAGE may aid in the removal neutralization of proinflammatory ligands. Lycopene has been shown to reduce seminal sRAGE levels 61 , illustrating a potential role in treating ROS-associated male infertility. Lycopene's effects are most likely an antioxidative course of action or from an increased...

Nonsteroidal Anti Inflammatory Drugs

Although most commonly known as treatment for pain relief and inflammation, nonsteroidal anti-inflammatory drugs (NSAIDs) have exhibited antioxidant effects in improving sperm quality and fertility in rabbits 94 . They function mainly through the reversible inhibition of cyclooxygenase, thereby inhibiting the production of prostaglandins and thromboxanes. Elevated prostaglandin levels have been found in men suffering from OAT 95 . Combination therapy of NSAIDs and carni-tine, which are thought to both undergo similar mechanistic pathways, may facilitate the beneficial results of NSAIDs therapy by suppressing excess prostaglandin production. Table 22.6 reviews recent studies conducted with NSAIDs on sperm.

Clinical Manifestations

free radicals energy metabolism Figure VIII. 102.1. Scheme illustrating the mechanism of MPTP toxicity at nigral dopamine neurons in primates. MPTP, which is lipophilic, enters the brain where it is transformed into MPP+ by monoamine oxidase B located in glial cells or in serotonergic neurons. MPP+ is taken up into the dopaminergic (DA) neurons, where it accumulates, by dopamine reuptake mechanisms. The binding of MPP+ to neuromelanin might assist in the accumulation of MPP+, or might contribute to its toxicity. MPP+ within the neurons is assumed not to undergo redox cycling to reproduce free radical species but, rather, to be actively accumulated by mitochondria, where it inerferes with mitochondrial energy metabolism, leading to cell death. The precise mechanism of MPP+ toxicity remains unknown. The sequence of events leading to MPTP toxicity can, in theory, be inhibited at a number of points (1) Selective monoamine oxidase B inhibitors (MAOI B) such as deprenyl inhibit the...

Protection Of Polymers From Photooxidation

A variety of additives are available for incorporation into polymers to act as antioxidants. A selection of these additives is listed in Table 8.2 together with the names of the polymers for which they are most suited. Whilst not an exhaustive list the compounds given in Table 8.2 do represent the major classes of antioxidant. One feature that is Table 8.2 Antioxidants used in j Compound clear from this Table is that these antioxidants tend to be effective in many different polymers, showing that they operate by interfering with the agents of photo-oxidation rather than by a specific interaction with the particular polymer. One general mechanism by which antioxidants act is by reaction with peroxy radicals. In doing so they compete with the polymer, thus reducing the extent to which the degradation mediated by peroxy radicals can occur. In the presence of appropriate hydrogen-donating antioxidants peroxy radicals undergo one of two propagation steps (Reaction 8.1 or 8.2). The rate...

Clinical Conditions Associated with OS 2431 Varicocele

The incidence of varicoceles in the general male population is 20 18 , while varicoceles are thought to be present in 40 of infertile males 19 . In males with secondary infertility, varicoceles are seen in 70-80 of patients 20 . Although the exact mechanisms through which varicocele damages spermatogenesis and sperm quality are not well understood, varicoceles have been associated with increased NO production 21 , intratesticular temperatures, and low antioxidant capacity 22 . NO is released by phagocytes and endothelial cells in the male reproductive tract 23 , In patients with varicocele, excessive NO is released by the dilated veins, which can lead to the dysfunction of spermatozoa 24 , Also, NO reacts with the superoxide anion and produce peroxynitrate, a strong oxidant that can negatively impact sperm function 25 . may play a role 26 . OS and other forms of damage associated with increased reactive oxygen and nitrogen species leads to infertility in 15 of males with varicocele 27...

Idiopathic Infertility

Infertile men are diagnosed with idiopathic infertility when normal sperm parameters and no other clinical condition that may result in infertility are seen. Oxidative damage may be a contributing factor to infertility in these normozoospermic males. While the exact cause of infertility may be unknown, idiopathic infertility has been correlated with higher levels of ROS and lower antioxidant levels than in fertile men 58 . A study found that men with idiopathic infertility had the second highest level of OS among the clinical diagnoses studied 44 . Therefore, it would be expected that infertile men diagnosed with idiopathic infertility would benefit from antioxi-dant treatments. Idiopathic infertility has also been associated with increased sperm

Subarachnoid Hemorrhage SAH

Cerebral vasospasm is the delayed narrowing of large capacitance arteries at the base of the brain after SAH, which is often associated with radiographic or cerebral blood flow evidence of diminished brain perfusion in the territory of the constricted arteries. About one half of patients with SAH have vasospasm, which may resolve or progress to cerebral infarction, and 15 to 20 percent of such patients die from vasospasm despite maximal therapy. y Angiographic vasospasm has a typical temporal course onset between 3 to 5 days after hemorrhage, maximal narrowing at 5 to 14 days, and gradual resolution over 2 to 4 weeks. y Oral nimodipine is recommended to reduce poor outcome related to vasospasm. Other calcium antagonists administered orally or intravenously are of uncertain value. So-called triple H therapy composed of hypertension, hypervolemia, and hemodilution is recommended. Aneurysms should be clipped when possible, and patients receiving this therapy should be closely monitored...

Environmental and Lifestyle Factors

Saleh et al. found a correlation between smoking and increased seminal leukocyte levels, as well as increased ROS production and lower antioxidant levels 60, 61 . Similarly, another study by Close et al. found a correlation between increased seminal leukocyte infiltration in cigarette-smoking men 37 . Additionally, high levels of sperm DNA damage have been reported in male smokers 60, 62 . This may be due to the mutagens and carcinogens associated with cigarette smoke 62 .Cigarettes contain nicotine, cotinine, hydroxycotinine, alkaloids, and nitrosamines, which are all sources of free radicals in the body 63 . Smoking has been associated with up to a 48 increase in leukocyte levels in semen, as well as up to a 107 increase in seminal ROS levels 60 .

Nanoparticles in air pollution

The ultrafine particles were proposed to be problematic due to their relatively large number per exposure mass and their small size (Donaldson et al. 2005). Ultrafine particles made from carbon and other low-toxicity materials were demonstrated to generate reactive oxygen species (ROS), which can either induce oxidative stress (depletion of antioxidants and oxidative damage of macromolecules) and or activation of intracellular signalling pathways that promote the production of cytokine proteins that drive inflammation. It is hypothesized that this ultrafine particle derived inflammation is sufficient to worsen the symptoms of pre-existing disease, leading to increased medication use, hospitalization, or even death.

Extracellular Superoxide Dismutases

The predominant site of production of ecSOD in the healthy vessel is vascular smooth muscle cells (Stralin et al. 1995), whereas in the atherosclerotic vessel the enzyme is produced by both vascular smooth muscle cells and macrophages (Fukai et al. 1998 Luoma et al. 1998). Of note, studies from other laboratories and our own indicate that endothelial cells do not produce ecSOD (Marklund 1990 Stralin et al. 1995). However, ecSOD binds to the heparan sulfates on the endothelial cell surface and has been found to be internalized by endothelial cells (Ohta et al. 1994). Thus, this potent antioxidant enzyme can be made by vascular smooth muscle cells and end up inside adjacent endothelial cells.

Neuropathology and Pathophysiology

Head trauma can result in a variety of neuro-chemical events (Novack et al. 1996). Excessive production of free radicals can affect cell membrane integrity and cause lipid peroxidation or attack cell organelles, such as the mitochondria. Excitatory amino acids can be harmful in excessive amounts, disrupting cell function and eventually resulting in cell death. Glutamate and aspartate, two common excitatory amino acids, have an affinity for receptors prevalent in the hippocampus and thalamus. The release of these amino acids is especially sensitive to hypoxic-ischemic events and increases dramatically after TBI, which may help explain the vulnerability of the hippocampus to the effects of TBI. The disruption of cellular calcium homeostasis by hypoxia-ischemia is another indirect source of brain injury. Hypoxic-ischemic insults interrupt normal ion pumping mechanisms and induce the release of in-tracellular calcium. In addition, the calcium influx triggers other chemical events,...

Reactive Oxygen Species

OS results from an impairment of a biological system's ability to reduce the formation of highly reactive species, repair detrimental damage, or reach a balance between ROS and antioxidants. Much research has focused on the etiology of OS, its link to male infertility, and its pathophysiological effects on male reproduction. Disturbances in reductases and functional redox state conditions disrupt cellular homeostasis. Numerous studies demonstrate a multitude of adverse effects induced by its causative factor ROS. Environmental toxicants have been verified to impair a cell's reductive environment by decreasing its reduction potential, leading to subsequent reverse catalysis by oxioreductases, and possibly damaging cell membrane proteins, lipids and DNA 27 . Even moderate levels of OS may trigger molecules to initiate a cascade of reactions, thereby inducing programmed cell death (apoptosis) 28 , There are two general forms of free radical species ROS and reactive nitrogen species...

Oxidative Stress in Benign Prostate Hyperplasia

Abstract The greatest risk factor for developing benign prostatic hyperplasia (BPH) is advanced age. Potential molecular and physiologic contributors to the frequency of BPH occurrence in older individuals include the oxidative stress, chronic inflammation, and alterations in tissue microenvironment. As BPH and aberrant changes in reactive oxygen species become more common with aging, oxygen species signaling may play an important role in the development and progression of this disease. Increased oxidative stress is a result of either increased reactive oxygen species generation or a loss of antioxidant defense mechanisms. Oxidative stress is associated with several pathological conditions including inflammation and infection. Oxygen species are byproducts of normal cellular metabolism and play vital roles in stimulation of signaling pathways in response to changing intra and extracellular environmental conditions. This review is aimed to explore the mechanism of oxidative stress in...

Aging Oxidative Stress and Prostate

Aging is associated with many metabolic disorders and with increased incidence of various cancers 50, 51 . Prostate cancer is a major age-related malignancy. Many theories have been formulated to explain the molecular and biochemical aspect of aging, but Harman in 1956 proposed free radical theory of aging in which the author suggested that the accumulation of damage to biomolecules caused by free radicals plays a major role in human aging 52, 53 . It is also believed that cellular oxidative stress increases with age and the increase in mitochondrial mutations can lead to further increase in ROS generation due to defective oxidative phosphorylation and electron transport 54 . Thus, it is possible that the increase in ROS leads to a self-perpetuating cycle with an ever-increasing oxidative challenge placed on the cells.

Role of Oxidative Stress in ED Unraveling the Molecular Mechanism

Abstract Many advances in the understanding of erection physiology and pathophysiology have been made in recent years. These advances have revealed the importance of oxidative stress and a complex interaction between oxidative stress and regulatory pathways in the penis in the development and progression of erectile dysfunction (ED) associated with various disease states. In this chapter, we present current knowledge of the pathophysiology of ED pertaining to the mechanisms of reactive oxygen species (ROS) production, the interaction between ROS-generating sources and the main regulatory pathways in the penis, the status of the antioxidant systems that reduce ROS bioavailability, and cellular targets for ROS action in vasculogenic and neurogenic ED. We further discuss a therapeutic strategy to improve erectile function in disease states by targeting specific ROS mechanisms in the penis.

Electron Spin Resonance Spectroscopy

Eumelanins were the first biological molecules studied by ESR spectroscopy. Commoner and coworkers (199) detected ESR signals in melanin and concluded that the paramagnetism was due to free radicals trapped in the pigment. Considerable attempts were made to correlate the free-radical properties with some alleged functions of melanins in the physiology of vision and in photoprotection (200). 2. Effect of Light on Free Radicals When melanins are irradiated with UV and visible light, an increased population of free radicals is generated, which has been detected by ESR spectroscopy. A more complex ESR spectrum with a shorter T1, a higher g-value, and a broader linewidth is produced. The transient free radicals consist of two components, one characterized by a low yield (ca. 1-2 ) and a decay time of a few seconds, and the other with a decay time of a few milliseconds, that accounts for about 50 of the signal (206). Under continuous irradiation, the yield of the latter component is 50-100...

Toxicity Amelioration

Amifostine (Ethyol-WR-2721) is a thiol that has been studied as a chemo- and radiotherapy-protectant agent. Briefly, this agent acts selectively as a scavenger of oxygen-derived free radicals in normal cells. The selective targeting effect of ami-fostine is at least in part related to the property of higher thiol uptake, due to vascularization and pH, demonstrated in normal cells rather than tumor cells. Although of theoretical concern, reports to date have not documented evidence of tumor protection .98 The potential role of amifostine was outlined in a randomized trial including 315 patients with advanced head and neck cancer treated with conventional radiotherapy with or without daily amifostine. The incidence of grade 2 acute and late xerostomia (assessed by saliva production measurement, questionnaire, and the Radiation Therapy Oncology Group RTOG clas

Physicochemical Properties and Biological Functions of Melanins

Natural melanins, although they hold an image of inert material due to their high insolubility, structural heterogeneity, and unusual spectral characteristics, possess some distinctive physicochemical properties of biological significance. For example, in biological systems, melanin can act as an electron-exchange polymer capable of protecting a tissue against redox reactions and trapping the free radicals which could disrupt the metabolism of living cells (200). Melanins thus protect the skin against the harmful UV radiations (226). Longuet-Higgins described melanin as a one-dimensional semiconductor with the protons acting as electron traps (227). In eyes, melanin acts as light screen and strongly resists light adaptation. Interestingly, unlike other alkaloids, reactions of insoluble melanins are heterogeneous in character and involve both the surface and the interior of the melanin particles. Moreover, in living systems, alkaloid molecules diffuse to receptor sites, while owing to...

Oxidative Stress in ED Associated with Cigarette Smoking

Cigarette smoke is a complex mixture of chemical compounds containing a high concentration of ROS, NO, peroxynitrite, and free radicals of organic compounds. These constituents get into the bloodstream and can directly activate vascular ROS production. In the general vasculature, cigarette smoking (or products of cigarette smoke) increases superoxide generation by both endothelial and smooth muscle cells from NADPH oxidase and uncoupled eNOS, and upregulates proinflammatory cytokines and the RhoA ROCK contractile pathway. This results in reduced NO bioavailability, increased vasoconstriction, and endothelial dysfunction 82, 83 .

Lessons from the Mouse GPx Knockout Models

Increased in the cauda epididymidis of GPx5- animals, reinforcing the idea that the tissue was facing an increase in H2O2 9 since catalase metabolizes only this substrate. These observations suggest that luminal ROS and especially H2O2 accumulate in the cauda compartment when GPx5 is no longer present. Despite the antioxidant response of the tissue, we have shown that the cauda epithelium of the GPx5- animals suffers oxidative injuries. This was also the case for the cauda-stored spermatozoa. In particular, cauda-stored spermatozoa in GPx5- animals showed a higher level of DNA oxidation, indicated by the increase in 8-oxo-deoxyguanosine residues (8-oxodG) associated with increased fragmentation and a slight nuclear decompaction state when compared to WT cauda-stored spermatozoa 9 . Although PRDX were not investigated in that study, it is possible that they also contributed to protect the cauda epididymidal epithelium and spermatozoa against the pro-oxidant situation generated in the...

Alzheimers Disease and Alzheimers Dementia

The oxidative stress hypothesis of neurodegeneration holds that free radical generation from metabolism is neurotoxic, and there is some evidence that Abeta may promote free radical formation.y This has led some to propose the use of antioxidants clinically and in experimental trials in patients with clinically diagnosed AD. y use of a large family of growth factor compounds that normally function during embryogenesis, some of which promote neuronal growth and retard neuronal death use of antioxidants to interfere with the generation of free radicals that cause cellular damage. Strategies for symptomatic therapy include

Testicular Torsion IR Injury in Testis and Oxidative Stress

Indeed, this causes further damage in the ischemic tissue and is known as reperfusion injury. Reperfusion after ischemia causes oxidative stress, which is characterized by imbalance between ROS and antioxidative defense system, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px). Although reinstitute of blood flow and oxygenation are very important to salvage affected testis, reperfusion may cause further damage paradoxically in the ischemic tissue. Thus, reperfusion injury may play an important role in testicular damage related to testicular torsion 108 . It has been postulated that gradual detorsion of torsioned testis has a tendency to decrease the degree of testicular reperfusion injury 108, 113 . Torsion (ischemia) and detorsion (reperfusion) of testis is an important phenomenon that has not been completely defined from the perspective of the signaling pathways. I R is associated with activation of neutrophils,...

Essential Oils Used In Animal Feed

Essential oils can be used in feed as appetite stimulant, stimulant of saliva production, gastric and pancreatic juices production enhancer, and antimicrobial and antioxidant to improve broiler performance. Antimicrobial effects of essential oils are well documented. Essential oils due to their potent nature should be used as low as possible levels in animal nutrition. Otherwise, they can lead to feed intake reduction, gastrointestinal (GIT) microflora disturbance, or accumulation in animal tissues and products. Odor and taste of essential oils may contribute to feed refusal however, encapsulation of essential oils could solve this problem (Gauthier, 2005). A total of 50 and 100 mg kg of feed of oregano oil* were tested on broilers. No growth-promoting effect was observed. At 100 mg kg of feed, antioxidant effect was detected on chicken tissues (Botsoglou et al., 2002a). Antioxidant activities of rosemary and sage oils on lipid oxidation of broiler meat have been shown. Following...

Sperm Oxidative Stress and DNA Damage

Many studies have reported the presence of reactive oxygen species within human spermatozoa and its consequences for the gamete 42-44 . From our understanding of the cell biology of human spermatozoa, it is perhaps no surprise that these cells are then susceptible to oxidative stress and DNA damage. The minute volume of cytoplasm in these highly specialised cells limits the antioxidant capacity usually afforded to other cell types. Once oxidative stress is initiated, fertilisation is compromised through the loss of motility and ability to fuse to the oocyte. These outcomes arise due to lipid peroxidation of the abundant redox-sensitive polyunsaturated fatty acids in the plasma membrane. These peroxides also have the capacity to further propagate oxidative stress by a lipid peroxidation cascade 45 . Oxidative stress also leads to a range of protein damage, including alkylation (by lipid peroxides products) and oxidation 46 . The sperm chromatin does not escape the negative effects of...

Clinical Conditions of Exacerbated Oxidative Stress That Lead to Sperm DNA Damage

An enhancement in oxidative stress, in addition to be determined by an increase in ROS production, may also be determined by a decrease in antioxidant defences 42 or both 43 , as it has been reported in men with varicocele. Moreover, the increase in seminal ROS levels seems to be correlated with varicocele grade 44 . This is a well-known factor that may induce DNA fragmentation either in vivo or in vitro 45 . Nitric oxide and peroxynitrite are produced in high concentrations in

Diagnosis of OS and ROS Levels

The chemiluminescence assay is a direct method of quantifying extracellular ROS levels. This assay uses lucigenin and luminol to assess the generation of the superoxide anion and hydrogen peroxide 76 . Lucigenin detects superoxide anion, while luminol detects hydrogen peroxide. These agents are oxidizable substrates that react with certain oxygen species in order to measure levels of ROS. The chemilumines-cence assay or calorimetric assay can also be used to measure the total antioxidant

Identification of Sperm Oxidative Stress from Clinical History

Male Infertility Causes Mnemonics

Has been linked with impaired spermatogenesis and increased sperm DNA damage 21-24 , Oral administration of phthalate esters to rats is reported to increase the generation of ROS within the testis and a concomitant decrease in antioxidant levels, culminating in impaired spermatogenesis 25 , Diabetes is an ever increasing endocrine cause of sperm oxidative stress as obesity levels increase in the Western population. Poor glycaemic control has been linked with excessive systemic production of ROS and an increase in sperm DNA fragmentation levels 26 , Further studies by this group confirmed that type I diabetes is associated with an increase in the oxidative DNA adduct 8-OHdG in sperm, confirming that diabetes induced oxidative stress is at least partially responsible for the decline in sperm DNA quality seen in diabetic men 27 . Furthermore, animal studies using the streptozotocin-induced diabetic rat model have found a significant increase in testicular oxidative stress within 6 weeks...

Molecular mechanisms of injury progression Figure

FREE RADICALS Free radicals in brain regions with low or intermittent blood perfusion, reactive oxygen species (ROS) are formed which produce peroxida-tive injury of plasma membranes and intracellular organelles 72 . The reaction with nitric oxide leads to the formation of peroxynitrate, which also causes violent biochemical reactions. Secondary consequences of free radical reactions are the release of biologically active free fatty acids such as arachi-donic acid, the induction of endoplasmic reticulum stress, the induction of mitochondrial disturbances and fragmentation of DNA. The latter may induce apoptosis and thus enhance molecular injury pathways related to mitochondrial dysfunction. The therapeutic benefit of free radical scavengers, however, is limited, as recently documented by the therapeutic failure of the free-radical-trapping agent NXY-059 73 .

Targeting Nadph Oxidase 281011 PDE5 Inhibitors

Several animal studies have demonstrated the beneficial effect of PDE5 inhibitors on reducing oxidative stress in the penis. Sildenafil citrate was found to decrease superoxide production in the penis of a mouse model of secondhand smoke-induced ED 91 . Sildenafil also decreases oxidative stress in rabbit penile vascular smooth muscle after exposure to several ROS-inducing agents such as nicotine 87 , TNFa 87 . combination of homocysteine and copper 129 , and vasoconstrictor thromboxane A2 mimetic 130 . This effect of sildenafil is apparently due to the inhibition of NADPH oxidase through the reduction in protein expression of its subunit p47phox 130 . Tadalafil also exerts a beneficial acute effect on the cardiovascular system by reducing serum levels of oxidative stress 131 in patients with ED. A vasorelaxant agent given in combination with PDE5 inhibitors proved more beneficial in reducing oxidative stress in the penis and improving penile erection compared to PDE5 inhibitors alone...

Effect of Varicocelectomy on Oxidative Stress

As discussed earlier, seminal ROS levels are higher in semen samples from infertile men with varicocele 53, 86, 87 (including men with normozoospermia 86, 88 ) than in controls and there are now several reports showing that varicocelectomy is generally associated with a reduction in seminal OS. However, the effect of varico-celectomy on seminal antioxidant capacity and seminal antioxidant enzyme activity (e.g., SOD) is mixed with some studies reporting lower and others higher antioxidant activity after varicocelectomy 58, 60, 89-93 (Table 18.3). Nevertheless, the true effect of varicocelectomy on seminal OS is not proven as most of the studies are retrospective and none are randomized, controlled trials. Table 18.3 Summary of studies that measured seminal OS and antioxidant (AOX) capacity before and after varicocelectomy Table 18.3 Summary of studies that measured seminal OS and antioxidant (AOX) capacity before and after varicocelectomy 8-OHdG 8-Hydroxy-2'-deoxyguanosine CAT catalase...

Influence of Cytokines on Sperm DNA and Apoptosis

Of sperm DNA seems to be an extremely important information for the prognosis of the male gamete fertilizing ability and may be an important step toward establishing new, additional diagnostic algorithms, which will pave the way to conservative treatment of male infertility (by antioxidants) as well as better qualification and selection of assisted reproduction techniques.

Clinicopathologic Correlations

Deficiency Vitamin Diseases

Vitamin C, or ascorbic acid, is a biologic antioxidant and free radical scavenger. The biosynthesis of bile acids, collagen, and norepinephrine, as well as the normal functioning of the hepatic oxygenase system, depends on these antioxidant properties. Vitamin C deficiency is rarely found in the United States. The classic deficiency state is known as scurvy. It is characterized by depression, fatigue, and widespread abnormalities in connective tissue. Oral lesions (including inflamed gingiva), petechiae, hemorrhage, impaired wound healing, hyperkeratosis, and bleeding into body cavities are commonly seen. Figure 5-7 depicts marked periodontal disease in two patients with scurvy. Figure 5-8 illustrates perifollicular purpura and ecchymoses in a patient with vitamin C deficiency.

Fecal Occult Blood Test

Gastric irritants such as aspirin, NSAIDs, and excessive alcohol consumption may also produce positive results. Oral iron supplements and acetaminophen do not affect the guaiac test. Ascorbic acid (vitamin C) in excess of 250 mg day or multivitamins with vitamin C may cause a false-negative result because ascorbic acid is a reducing agent and interferes with the oxidation of guaiac. Other antioxidants should also be avoided. Antacids may also cause false-negative results.

Biomarkers for Inflammation in BPH

COX-2 overexpression was also higher in PIN and poorly differentiated tumors 122, 132, 136, 140 . Chronic inflammation also produces a free radical substance oxidative stress such as inducible nitric oxide (iNOS) reactive nitric species (RNS) and various reactive oxygen species (ROS) 119, 123, 135, 141, 142 , These oxidative stresses can induce vascular tissue damage, protein structural and functional damage, and genomic damages and cause posttranslational modifications including those involved in DNA repair and apoptosis 119 . These can lead to oxidative DNA damage such as point mutations, deletions, or rearrangements and reduce DNA repair. These oxidative stresses also alter the stem cell population. Genomic alterations in cellular DNA result in the modulation of an imbalance between cell proliferation and cell death. A change in the normal regulation of programmed cell death leads to hyperplastic or precancerous transformation 122, 124, 143 . All of these...

Copper Silver and Gold

Toxic Groups Drug Design

The human variant of the antioxidant enzyme, superoxide dismutase, contains both copper and zinc (Figure 10.14). The toxic superoxide anion, O-, is sometimes deliberately produced by organisms for particular objectives. Thus, some phagocytes, which are part of the immune system in higher organisms, produce large quantities of superoxide together with peroxide and hypochlorite by means of oxidases in order to kill invading microorganisms. In unfortunate cases this protection system may fail giving rise to certain autoimmune diseases like rheumatoid arthritis. Under these circumstances, the superoxide dismutase enzyme is administered as an anti-inflammatory pharmaceutical. The same therapy is consistently applied during open heart surgery in order to protect the tissue against oxidative attack by the superoxide radical. Free radical formation caused by metal ions like Cu(II) results in a continuous production of cytotoxic species leading to loss of dopaminergic neurons associated to PD....

Various Transporter Defects Hartnups Disease

Menkes' disease, an X-linked disorder in which insufficient intestinal absorption of copper leads to deficiency of copper-requiring enzymes, is now known to be due to a gene located at Xq13.3. y The gene product belongs to a highly conserved family of cation-transporting ATPases, which function in the transport of ions across cellular and intracellular membranes. The low serum copper levels, the high tissue levels (particularly intestinal mucosa, except liver), and studies from patients' cultured cells strongly suggest that the basic pathogenetic defect is the failure of a plasma membrane pump that usually extrudes copper from cells or the failure of a pump that ordinarily transports copper into an intracellular organelle-like endoplasmic reticulum. Deficient activity of copper-requiring enzymes explains the symptoms and signs. Deficiency of dopamine beta-hydroxylase, critical to the catecholamine synthesis pathway, may be related to autonomic abnormalities due to decreased...

Inflammatory Conditions in the Gonad Oxidative Stress

Oxidative Stress And Female Infertility

Exogenous antioxidants polyphenols, vitamin C, vitamin E and carotenoids Fig. 9.3 Oxidative stress as a link between inflammation and apoptosis. The inflammatory state induces activation of macrophages and release of cytokines leading to free radicals (ROS). ROS leads to damage of plasma membranes, DNA, and other cell structures. Inflammation causes transfer of NF-kB to cell nucleus and trigger transcription of death genes and apoptosis or pro-proliferative genes (cytokines) Exogenous antioxidants polyphenols, vitamin C, vitamin E and carotenoids Fig. 9.3 Oxidative stress as a link between inflammation and apoptosis. The inflammatory state induces activation of macrophages and release of cytokines leading to free radicals (ROS). ROS leads to damage of plasma membranes, DNA, and other cell structures. Inflammation causes transfer of NF-kB to cell nucleus and trigger transcription of death genes and apoptosis or pro-proliferative genes (cytokines) The Sertoli cells protect seminiferous...