12 Healthy Foods High in Antioxidants

Antioxidants from fruits and berries overview

Fruits and berries are good sources of antioxidants, including carotenoids, ascorbic acid, tocopherols, flavonoids and phenolic acids. It has been known for a long time that the phenolics, as well as some of the other antioxidant components, are closely associated with the sensory attributes of fresh and processed fruits, berries and other plant foods. Especially, the contribution to colour by carotenoids (yellow to orange and red) and anthocyanins (red to purple and blue) is well known. Also the specific involvement of some of the phenolic substances in flavour development and taste sensation is amply documented.1 Phenolic compounds, including those having potent antioxidant activity, are also substrates for undesirable, oxidative browning reactions occurring during bruising of fruits, when fruits are cut or during their processing. The possible beneficial biological functions of the traditional antioxidant vitamins, i.e. ascorbic acid, a-tocopherol and to a certain extent...

Antioxidants from vegetables overview

The antioxidants present in commonly consumed vegetables include ascorbic acid, tocopherols, carotenoids and phenolic compounds such as flavonols and phenolic acids (Table 3.3). In comparison to fruits and berries, vegetables generally contain much lower amounts of antioxidant compounds. A large amount of vitamin C is found in sweet red pepper (1850mgkg-1) and significant amounts in Brussels sprouts (up to 900mgkg-1) and broccoli (750-830 mg kg-1), while Table 3.3 Antioxidant compounds in selected vegetables and their products, mgkg fresh weight Table 3.3 Antioxidant compounds in selected vegetables and their products, mgkg fresh weight the amounts of vitamin E are generally below 10mgkg-1 in vegetables. According to Hussein et al.68 although there was significant loss in vitamin C during storage of broccoli and green peppers, in most cases there was no difference in loss of vitamin C or beta-carotene between the processed and unprocessed vegetables, and the packaging systems. After...

Dietary prevention of sudden cardiac death SCD the role of dietary fatty acids alcohol and antioxidants

We now examine whether diet (and more precisely, certain dietary factors) may prevent (or help prevent) SCD in patients with established CHD. We focus our analyses on the effects of the different families of fatty acids, antioxidants and alcohol.2 Support for the hypothesis of a clinically significant antiarrhythmic effect of n-3 PUFA in the secondary prevention of CHD, as put forward in DART,3 came from two randomised trials testing the effect of ethnic dietary patterns (instead of that of a single food or nutrient), i.e. a Mediterranean type of diet and an Asian vegetarian diet, in the secondary prevention of CHD.18'19 The two experimental diets included a high intake of essential alpha-linolenic acid, the main vegetable n-3 PUFA. Whereas the incidence of SCD was markedly reduced in both trials, the number of cases was very small and the antiarrhythmic effect cannot be entirely attributed to alpha-linolenic acid as these experimental diets were also high in other nutrients with...

Oxidized Fatty Acids A Autoxidation and Antioxidants

Autoxidation is facilitated by pro-oxidants and inhibited by antioxidants. Pro-oxidants, such as metals or other radical initiators, operate by promoting the initiation step or else they may inhibit the activity of antioxidants. Antioxidants are frequently added to fats and fat-containing foodstuffs to prolong shelf life (108). These are often phenolic compounds which act by interferring with the propagation sequence by conserving propagating radicals into nonpropagating species (109, 110). Their effectiveness is often increased by compounds such as citric acid, ascorbic acid, or phosphoric acid (called synergists). In this regard, there is considerable evidence for a contributory, antioxidant role for vitamins E and C and the carotenoids constituents of fruit, vegetables, beverages, and grains in the maintenance of health and the protection from coronary heart disease, cataracts, and certain cancers (111). Recent work indicates possible important roles of polyphenolic components (the...

Effect of different processing technologies on antioxidant activity

Food processing involves changes in structural integrity of the plant material and this produces both negative and positive effects. When the negative and positive effects counterbalance each other, no change in the antioxidant activity occurs.115 The antioxidant activity is diminished owing to inactivation of antioxidant compounds caused by oxidation, for example, by enzymes (polyphenoloxidase and others) or leaching into the cooking water. Both negative changes have a greater impact on the water-soluble antioxidants, vitamin C, flavonoids and phenolic acids, than on the lipid-soluble antioxidants, carotenoids and tocopherols. The positive effects of food processing include transformation of antioxidants into more active compounds, such as the deglycosylation of onion quercetin,106 as well as an increase in the antioxidant activity owing to inhibition of enzymes.81 Peeling and juicing result in substantial losses of carotenoids, anthocyanins, hydroxycin-namates and flavanols as the...

Microcomponents antioxidants and vitamins

Ripe tomatoes are relatively rich in antioxidants vitamin C (160-240mgkg-1), lycopene (30-200mgkg-1), provitamin A carotenes (6-9mgkg-1) and phenolic compounds flavonoids (5-50mgkg-1) and phenolic acids (10-50mgkg-1).14 Also present in small quantities are vitamin E (5-20 mg kg-1) and trace elements such as copper (0.1-0.9mgkg-1), manganese (1-1.5mgkg-1) and zinc (1-2.4mgkg-1) which are present in several antioxidant enzymes. Most often the tomato variety is not indicated and the reported values are a mean concentration of the constituents in tomatoes found in local markets.

Antioxidants cardiovascular disease and oxidative modifications of lowdensity lipoprotein

Both lipid-soluble and water-soluble antioxidants present in blood may be important in preventing cardiovascular disease owing to their ability to prevent the oxidation of lipid-protein complexes called lipoproteins. Lipoproteins are extremely important in cardiovascular disease since we know with certainty that high levels of LDL-C cause atherosclerosis, which is the underlying cause of most cardiovascular disease. In contrast, high levels of HDL-C are a negative risk factor for CVD. Atherosclerosis is the gradual build-up of 'plaque' in the arterial wall. LDL-C is the major source of the lipids occurring in these plaques. LDL is the primary plasma carrier for both vitamin E and CoQIO, both of which act as antioxidants in LDL by inhibiting lipid peroxidation of lipids containing polyunsaturated fatty acid moieties. Work by Jessup et al. (199O) indicates that most of the endogenous vitamin E in LDL must be oxidized before it is converted into a 'high uptake' form of oxLDL capable of...

Vitamin D as an antioxidant

Work by Wiseman (1993) has shown that vitamin D3 (cholecalciferol), its active metabolite 1,25-dihydroxycholecalciferol, Vitamin D2 (ergocalciferol), and 7-dehydrocholesterol (pro-Vitamin D3) are all membrane antioxidants by virtue of their abilities to inhibit iron-dependent liposomal lipid peroxidation. There are very few studies focusing on the potential role of vitamin D as an antioxidant in biological systems. One such study by Sardar et al. (1996) found that vitamin D3 may function as an in vivo antioxidant in the rat liver with an effectiveness higher than that observed with vitamin E supplementation. It is unlikely that vitamin D in plasma could be an effective antioxidant since its levels are very low, i.e. the levels of 25 (OH)D3 and other vitamin D metabolites in healthy persons are between 6O and 1OOnM. In contrast, plasma vitamin E levels are between 15 3O y M, which is at least 25O times higher than the typical plasma levels of vitamin D. At present, there are no data...

Ubiquinol as an antioxidant

The role of ubiquinol as an antioxidant is much more controversial than its role in ATP synthesis (Beyer, 1992). In liposomes, ubiquinol has antioxidant ability similar to that of alpha-tocopherol but, unlike alpha-tocopherol, is not recycled by vitamin C (ascorbate) (Frei et al., 199O Shi et al., 1999). There is, however, evidence suggesting that the semiquinone form of CoQ1O may be a pro-oxidant and generate superoxide radicals (Beyer, 1992). In vitro data suggest, however, that CoQ1O can conserve vitamin E in rat liver microsomes and mitochondrial membranes and thereby increase the resistance of these membranes to oxidative damage (Hiramatsu et al., 1991). Dietary supplementation with CoQ1O is known to increase the level of ubiquinol in LDL and to increase the resistance of LDL to the initiation of lipid peroxidation (Mohr et al., 1992). As detailed above, the ability of dietary antioxidants to prevent the formation of oxLDL may be an important factor in preventing the very early...

Production of free radicals in ischemiareperfusion

Free radicals are atomic or molecular structures with one or more unpaired electron in the outermost orbital. Such unpaired electrons make these species very unstable and therefore quite reactive free radicals tend to react with other molecules to pair this electron and thereby generate a more stable species. Ground state molecular oxygen is a bioradical with its two outermost valance electrons occupying separate orbitals with parallel spins. Pairs of electrons typically have opposite spins, and thus fortunately impose a restriction on the reaction of molecular oxygen with most organic molecules. However, ground state oxygen may be converted to the much more reactive ROS (reactive oxygen species) forms by energy transfer (- singlet oxygen) or by electron transfer reactions (superoxide, hydrogen peroxide and hydroxyl radical). The equilibrium between production and scavenging of ROS may be perturbed by a number of factors and disease states16'17. ROS recently have been related to...

Vitamin E and other antioxidants in the prevention of cardiovascular disease

Although enzymatic and nonenzymatic oxidation of LDL seems to be involved, its relevance in the evolution of human atherosclerosis is still unclear. An important matter of discussion is the evident discrepancy between experimental and clinical trials with antioxidants, that, in fact, provided divergent results. Most trials with antioxidants in experimental models of atherosclerosis demonstrated that this treatment is able to retard the progression of atherosclerosis while the results of clinical trials are conflicting,5 in that positive as well as negative effects has been reported. The investigation of antioxidants for prevention of atherosclerosis stems from observational trials that demonstrated the existence of an inverse relationship between the consumption of antioxidant vitamins and the risk of cardiovascular events. However, meta-analysis of the observational studies indicated that among antioxidant vitamins, vitamin E was the only one that exerted a beneficial effect against...

Dietary antioxidants and the prevention of CHD epidemiological evidence

A large number of epidemiological studies have evaluated potential relationships between dietary intake of antioxidants and coronary heart disease (CHD). These are summarised in Table 5.1. Among these, the Nurses' Health study,36 included over 87 000 female nurses 34 to 59 years of age, who completed dietary questionnaires that assessed their consumption of a wide range of nutrients, including vitamin E. During follow-up of up to 8 years 552 cases of major coronary disease were documented. As compared with women in the lowest fifth of the cohort with respect to vitamin E intake, those in the top fifth had a relative risk of major coronary disease of 0.66 after adjustment for age and smoking. Further adjustment for a variety of other coronary risk factors and nutrients, including other antioxidants, had little effect on the results. Similarly, the Health Professionals' Follow-up study, among almost 40 000 males of 40-75 years, followed up for four years, showed a lower risk of coronary...

The Role Of Antioxidants For Dna Protection

Next to to enzymatic antioxidants some vitamins have an important antioxidative effect, e.g vitamin E and C52, 53, 54. Vitamin E is located in lipoproteins and membranes where it interrupts the radical-induced chain reaction of lipidperoxidation. Vitamin C has a double function. First, it is needed to restore Vitamin E, which is transferred from alpha-tocopherol during the above-mentioned reaction to the tocopherol radical, and second, it has radical savaging properties as well. Exogenous antioxidants were also investigated with respect to their ability to blunt or even to completely prevent the oxidative damage to the DNA as described above, and at least with respect to clinical HBO therapy the question still remains unsettled whether antioxidant supplementation allows to prevent HBO-induced geno-toxicity both vitamin E and the synthetic antioxidant N-acetylcysteine failed to affect the HBO-induced DNA damage in healthy volunteers55, but no data are available in patients with...

Dietary antioxidants and the prevention of CHD evidence from clinical trials

While most epidemiological studies have demonstrated that dietary intake of vitamin E is inversely related to coronary heart complications, supplementation studies gave conflicting results. Clinical trials with antioxidants have been done in patients with or without previous history of cardiovascular disease (Table 5.2). Surrogate endpoints, such as analysis of atherosclerosis progression, or 'hard' endpoints, such as vascular death and MI, have been used to evaluate the clinical benefits of antioxidant vitamins. The Alpha-Tocopherol-Beta-Carotene-Cancer (ATBC)52 prevention study was a randomized, double-blind, placebo-controlled primary-prevention trial to determine whether daily supplementation with alpha-tocopherol, beta-carotene or both reduced the incidence of lung cancer and other cancers. A total of 29 133 male smokers, 50-69 years of age, were randomly assigned to one of four regimens alpha-tocopherol (50 mg per day) alone, beta-carotene (20 mg per day) alone, both...

Longer Life Expectancy In Organisms Belonging To The Same Cohort Group Is Associated With Relatively Higher Levels Of

All houseflies lose the ability to fly prior to death. Therefore, in an aging population, shorter-lived flies can be identified as flightless ''crawlers'' in contrast to their longer-lived cohorts, the ''fliers.'' The average lifespan of crawlers is about one-third shorter than the fliers. Levels of antioxidant defenses (superoxide dismutase (SOD), catalase (CAT), and glutathione) and products of

Phenolic antioxidants

A large variety of phenolic phytochemicals that have several beneficial functions on human health are present in plants and especially in fruits. The phenolic phytochemicals are generally present in their glycosidic and nonglycosidic forms. The glycosides are mainly confined to hydrophilic regions in the cells, such as in vacuoles and apoplasts, probably because of their higher water solubility (197,198). Glycosylation of the hydroxyl groups on the phenolic ring of a phenolic phytochemical renders the molecule more water soluble and less reactive toward free radicals (6). Glucose is the most commonly involved sugar in glycoside formation, although phenolic glycosides of galactose, rhamnose, xylose, and arabinose and disaccharides such as rutinose, have also been reported in plants (6). Polymeric phenolics such as tannins exist primarily as condensed tannins or proanthocyanidins and are formed biosynthetically by the condensation of single catechins and flavonols. They are present...

Of host antioxidant response

Investigations so far in food grade clonal herb systems (1) and legume sprouts (112-114) led to the development of the model that activity of CCP, proline linked pentose-phosphate pathway is important for stress induced phenolic biosynthesis such as RA and phenolics and that this stimulation of phenolics is likely closely linked to stimulation of antioxidant response pathways (Figure 8.4) (96,112-114). Further research has indicated that the proline biosynthesis pathway coupled to stress induced antioxidant response pathways could be also stimulated in legume sprouts using exogenous treatment of phenolic extracts from clonal oregano (113,115,116). Phenolic extracts from these clonal oregano lines have high free radical scavenging activity (47). Proline linked stimulation of antioxidant enzyme response pathways may also be stimulated by low pH and salicylic acid (117). Further, exogenous seed treatment with oregano phenolic antioxidant extracts enhanced endogenous phenolic content, GPX...

Plant phenolics in human health and as antioxidants

It is evident that plant phenolic compounds constitute one of the most numerous and widely distributed groups of substances with more than 8000 phenolic structures currently known (28). In addition to stress linked phenolics coming only from the shikimate and phenylpropanoid pathways, a number of the phenolic compounds are found in plants, including the flavonoids that contribute to the characteristic flavor and fragrance of vegetables, fruits, tea, and wine. These compounds, which come from phenylpropanoid and polyketide (acetate-malonate) pathways, also have biological properties that are beneficial to human health. Flavonoids such as quercetin and catechin and isoflavonoids, genistein for example, are being investigated for properties which may reduce the incidence of cancer (22,23). Flavonoids and isoflavonoids are a class of phenolic compounds that have appeared sequentially during plant evolution and are simple aromatic compounds generated from both the phenypropanoid and...

Antioxidant Assays Based on Free Radical Neutralization

Many antioxidant assays are based on their ability to neutralize or quench free radicals. The two free radicals that have been most commonly used for assessing antioxidant activity are 1,1-diphenyl-2-picrylhydrazyl (DPPH) (43,44), and acid) (ABTS) (45,46) (Figure 10.3). The DPPH free radical is a stable radical with one electron delocalized over the molecule (Figure 10.3). This delocalization gives a deep purple color with absorption maxima at 517 nm in an ethanol solution (43,44). When an antioxidant capable of donating a hydrogen reacts with the DPPH radical it gives rise to a nonradical reduced form of DPPH which has a yellow color. The decrease in the absorption is measured spectrophoto-metrically and is compared with an ethanol control to calculate the DPPH free radical scavenging activity (43,44). This method is a very quick and simple method for the measurement of antioxidant activity. The antioxidant capacity in this assay depends on the chemical structure of the antioxidant...

Hypoxia Free radicals Reperfusion Injury RI HBO

Hypoxia, through the interruption of aerobic metabolism, initiates catabolism of ATP to adenosine creating anaerobic metabolites like hypoxanthine an electron donor which in the presence of oxygen mediates the formation of free radicals superoxide anion, and hydroxid peroxide or hydroxyl radical (if more electrons are added). The resumption of blood flow after a prolonged period of flow cessation causes an inflammatory reaction in the microcirculation the so-called ischemia reperfusion injury, (RI) or no-reflow phenomenon where the free radicals play an important role17. The restoration of perfusion and oxygen delivery to hypoxic tissues after a certain period of ischemia normally should be related with reestablishment of aerobic metabolic balance and depletion of free radicals but instead of it far greater production of reactive oxygen intermediates may occur18. A cascade of interactions is induced by the action of free radicals, molecules highly unstable, upon the cellular membranes...

Antioxidants CellSupporting Agents

A number of theories as to what causes PD at the cellular level include oxidative stress and free radical formation, mitochondrial impairment, intracellular protein clumping, inflammation, apoptosis (programmed cell death), and excitotoxicity (5). Many of the prescribed supplements, minerals, and vitamins by alternative practitioners are based upon these theories and the belief or hope that cellular function will be restored and or future brain cell injury prevented with their use. Currently, there is little if any scientific study to support the use of most of these supplements in the treatment of PD and it is critical to acknowledge that their use specifically for the treatment of PD is based upon theory only and not upon evidence-based clinical research. Despite the lack of research supporting their use for PD, some of these, in particular, the antioxidants that control potentially damaging free radicals or support mitochondrial function may hold the greatest promise for finding a...

Relevance of phenolic antioxidants for functional food and comparative metabolic biology considerations

It is clear that food plants are excellent sources of phenolic phytochemicals, especially as bioactives with antioxidant property. As is evident, phenolic antioxidants from dietary sources have a history of use in food preservation, however, many increasingly have therapeutic and disease prevention applications (69-72). Therefore, understanding the nutritional and the disease protective role of dietary phytochemicals and particularly phenolic antioxidants is an important scientific agenda well into the foreseeable future (73). This disease protective role pf phytochemicals is becoming more significant at a time when the importance of in the prevention of oxidation linked chronic diseases is gaining rapid recognition globally. Therefore, disease prevention and management through the diet can be considered an effective tool to improve health and reduce the increasing health care costs for these oxidation linked chronic diseases, especially in low income countries. As discussed earlier,...

Antioxidant Activity

Why would copper associated with the prion protein at the synapse be of any benefit Since 1996, there has been increasing evidence that the prion protein increases cellular resistance to oxidative stress (64). Cerebellar neurones and astrocytes from PrPC knockout mice are more sensitive to superoxide toxicity (32,34). Additionally, there is evidence from cell culture models that toxicity of PrPSc involves oxidative stress, as blocking toxicity of the neurotoxic peptide mimic of PrPSc can be achieved with antioxidants (65). Cultured cells infected with PrPSc are also much more sensitive to oxidative assault than noninfected cells (66). Our laboratory also has evidence that when N2A neuro-blastoma cells are transfected to overexpress PrPSc they show increased resistance to the toxicity of superoxide. However, when those cells are infected so that they express large amounts of PrPSc instead they are more sensitive to superoxide toxicity (Fig. 3). More recently, there is evidence that...

Antioxidants

Free radical production is enhanced in both the ischemic core and penumbral following stroke injury, and this is believed to cause much of the damage seen in the core as well as penumbra. There are many agents that either block free radical production or inhibit its activation that have been shown to be very effective in experimental models. Uric acid is a well-known natural antioxidant present in fluids and tissues. Administration of uric acid resulted in a highly significant reduction in ischemic damage and improved behavioral outcome (Yu et al., 1998). Edaravone, Tetramethylpyrazine, alpha-phenyl-N-tert-butyl-nitrone, FR210575, and NXY-59 are other free radical inhibitors that were effective against experimental stroke injury. EGb-761 is a free radical scavenger derived from a concentrated extract of Ginkgo that is currently in a phase 2 clinical trial (Legos et al., 2002). Clinical trials with free radical scavengers have had limited success after acute ischemic stroke, but have...

International Variation In Rates

In their systematic review of cancer causation, Doll and Peto7 placed the majority of the unexplained excess of cancer observed in migrating populations on dietary factors acting directly or indirectly through their potential impact on lifestyle factors (e.g., reproduction, exercise). During the past 20 years, there has been a concerted effort by epidemiologists and experimentalists to verify the role of dietary factors in the etiology of cancer. Much of this effort has been directed toward proving the detrimental effects of dietary fat and the potential protective effect of a wide range of dietary antioxidants.8 Unfortunately, it now seems likely that dietary factors are directly related to only a relatively small number of cancers, primarily, and not surprisingly, those of the digestive tract (esophagus, stomach, and large bowel). At the same time, it appears increasingly likely that the majority, if not all, of the hormone-related cancers have little direct relationship to any...

Functional foods defined

Functional foods that are marketed with claims to reduce heart disease focus primarily on the risk factors of blood cholesterol, homocysteine and hypertension. This can be done by a reduced content of food components that are known to increase risk, such as saturated fat or sodium. More recently products have been designed that are enriched in components that are thought to reduce risk. The most common 'protective' ingredients include fibres, soya, omega-3 fatty acids, phytostanols and phytosterols, and (antioxidant) vitamins. These components have cholesterol or homocysteine-lowering abilities in metabolic studies. The added ingredients may be food components that are often deficient in Western diets, such as calcium and folate. Their recommended intake could, however, be achieved by 'normal' foods. The added ingredients may also be nutrients or phytochemicals that are normally

New Opportunities for PCA Prevention

The convergence of PCA epidemiology, indicating a possible role for prostate inflammation, and a significant role for the diet, in PCA development, with molecular pathology, revealing that neoplastic prostate cells may have acquired an increased vulnerability to carcinogen damage, provides an opportunity for the discovery and development of rational new approaches to PCA prevention. Possible strategies include reduced exposure to genome damaging oxidants and other carcinogens, and intake of antioxidant micronutrients, including vitamin E, selenium, and carotenoids such as lycopene, which may be able to intercept reactive oxygen species before they inflict genome damage in the prostate. Administration of anti-inflammatory agents, when distributed into prostate tissues, may reduce oxidant production by prostate inflammatory cells. Consumption of cruciferous vegetables, containing the isothiocyanate compound, sulforaphane, an inducer of GSTs and other carcinogen-detoxification enzymes,...

Health benefits of whole foods over isolated components

There are many claims made in the media and promotional literature about the qualities and benefits of specific (or groups of) compounds found in fruits and vegetables. We are told that wrinkles, absentmindedness, cancer and clogged arteries (among many other disorders) can be prevented, or alleviated, by consuming these compounds in the form of isolates or concentrated extracts. In such claims the words 'tested', 'effective', 'safe', 'essential' and 'proven' are freely used. In the world of nutritional science, however, the picture is not so clear. The following two quotes provide an example of this apparent contradiction. The first relates to a study of antioxidant vitamins and risk factors for cardiovascular disease, 'These results back-up the findings of previous studies and point to a positive role for antioxidant supplementation among those suffering from coronary artery disease'.25 The second statement is again related to antioxidants and chronic disease, 'Current evidence is...

The use of functional foods to meet dietary guidelines

Foods enriched with fibres and vitamins can be an alternative to fruits and vegetables, but only to a certain point. For example, different dietary fibres have different effects on CVD risk water-soluble dietary fibres such as pectin and guar gum appear to have stronger effects than insoluble fibres such as wheat bran.24,25 Thus, a mixture of various dietary fibres such as found naturally in fruits and vegetables appears to be necessary for a protective effect on CVD. Also, adding vitamins to foods to compensate for low fruit and vegetable intakes might not have the expected effects. For example, beta-carotene was widely believed to reduce cancer risk in smokers, because intake of carotene-rich foods was associated with less cancer, as were high levels of carotene in blood. However, it was found that carotene supplements increased risk of lung cancer in smokers.26 27 Large clinical trials of antioxidants have also had disappointing outcomes.28 Moreover, several other bioactive...

Disruption of intestinal mucosal barrier

Mucosal organisms or their breakdown products may permeate the intestinal wall if the mucosal barrier function is breached. This barrier may be compromised by many pathological states and processes. The mucosa at the tip of the villi are particularly prone to ischaemia due to the counter-current exchange mechanism of the vessels. Shunting of blood during low flow states may lead to ischaemia affecting the tips of the villi alone. Subtle mucosal damage, which is only detectable microscopically, may occur following mild ischaemia. In transient hypoperfusion or hypoxia, the mucosal injury is more pronounced during reperfusion when the oxygen supply is re-established. This is due to damage by the putative deleterious oxygen radicals which are generated mainly via the xanthine oxidase pathway. Xanthine oxidase occurs naturally as the dehydrogenase but in ischaemia it is converted by proteolysis to the oxidase form. This latter form then catalyses a reaction which utilizes oxygen to convert...

Ischaemiareperfusion injury

This phenomenon is not confined to the bowel as other organs and systems may also suffer when a reduction in blood flow is followed by revascularization or successful resuscitation. The release of mediators initially causes regional damage but with spillage into the systemic circulation other organs or systems are affected. Ischaemia-reperfusion injury to the lower limb may lead to non-cardiogenic pulmonary oedema and changes in intestinal morphology. Similarly, reperfusion of ischaemic bowel may damage the liver parenchyma and lungs. Such local and remote organ injuries may be abrogated by pretreatment with ibuprofen and mannitol, suggesting that the generation of oxygen-derived free radicals and the activation of the arachidonic acid cascade have important roles to play.

Purification and characterisation of proteins

Once in the lab, the tissue needs to be disrupted. This is a critical step Cells should be broken open, but cell organelles should remain intact. Usually the tissue is minced first by hand, then cut into a fine pulp by rotating knifes (for example in a Warring blender like those used to make milk shakes in the kitchen) and finally homogenised by the application shearing forces in specialised equipment (Potter-Elyehjem- or DoUNCE-homogeniser, French press). All these steps are performed on ice, buffer solutions are used to keep the pH at the required value, they usually also contain protease inhibitors, antioxidants and sucrose or mannitol to keep the osmotic pressure in the solutions at the same level as in the cell ( 300-350 mosm). Ions like Na+,

Differing types of claim nutritional and health claims

All these types of nutrition claim are based on established knowledge of nutrients and their physiological functions, which must be widely accepted by the scientific community. So-called 'enhanced function' (functional) claims and reduction of disease-risk or health claims are particularly important for functional food. These types of claims relate to specific beneficial effects of foods or food components, whether nutrients and non-nutrients. Enhanced function or functional claims describe the beneficial effects of food components on physiological or psychological functions, metabolic activities, cellular and biochemical process, beyond the established role of these foods in normal functions of the body. These claims do not refer directly to any healthy benefits or disease risk reduction. Examples of claims of enhanced function are 'calcium improves bone density', 'antioxidants reduce the risk of oxidative stress', 'folate helps reduce plasma homocysteine levels', 'non-digestible...

Project Title Alcohol Induced Immunomodulationretroviral Cardiopath

Summary Cardiomyopathy and left ventricular dysfunction are prevalent in people with AIDS or chronic alcohol use. However almost nothing is known of the combined effects of retroviral infection plus alcohol on heart disease. Our murine retrovirus infection mimics much of the cytokine dysregulation found during HIV infection, prompting inflammatory damage for cardiac toxicity. We found that alcohol consumption exacerbated many immune, oxidative, and nutritional defects due to murine retrovirus infection. We found that alcohol + retrovirus exposure was particularly toxic, increasing Th2 and reducing Th1 cytokines, dramatically lowering cardiac vitamin E, increasing oxidation of cardiac lipids and synergistically promoting severe heart damage due to Coxsackie B3 infection. Our overall hypothesis is that the combination of ethanol + retroviral infection induces immune dysfunction and oxidation for increased cardiovascular disease. These effects should promote growth and pathogenesis of...

Phenolic Synthesis In Seed Sprouts

Preliminary results (1,69,72,133,134,148) have provided empirical evidence for a link between proline biosynthesis and oxidation, as well as stimulation of G6PDH. In light mediated sprout studies in pea (Pisum sativum), acetylsalicylic acid in combination with fish protein hydrolysates (a potential source of proline precursors) stimulated phenolic content and guaiacol peroxidase (GPX) activity during early germination with corresponding higher levels of proline and G6PDH activity (149). In parallel light mediated studies in pea, low pH and salicylic acid treatments stimulated increased phenolic content and tissue rigidity. Similarly, there was concomitant stimulation of G6PDH and proline (148). This work supported the hypothesis that pentose-phosphate pathway stimulation may be linked to proline biosynthesis and that modulation of a proton linked redox cycle may also be operating through proline linked pentose-phosphate pathway (148). In dark germinated studies in pea, high...

Summary of strategies and implications

Techniques for phenolic phytochemical enhancement for functional food design is based on harnessing the potential of proline linked pentose-phosphate pathway (PLPPP) as the critical control point (CCP) in clonal shoots of single seed genetic origin such as herbs from the family Lamiaceae and seed sprouts in self-pollinating species such as various legumes. This strategy can be extended to develop foods with better phenolic phytochemical profile and functionality. Further it can be extended to develop functional foods and supplements with consistent ingredient profiles targeted against a disease condition. This concept is now being extended to specifically isolate antioxidants for diverse disease conditions, antimicrobials against bacterial pathogens, phytochemicals for diabetes management, angiotensin converting enzyme inhibitors for hypertension management, l-DOPA for Parkinson's management, dietary cyclooxygenase (COX-2 inhibitors) for inflammatory diseases and isoflavones for...

Natural Models Of Alzheimerlike Pathology

Af3 accumulation correlates with behavioral impairments in aged dogs (Colle et al., 2000), and with a regional loss of brain substance (particularly in the frontal lobes) beginning around 8 years of age (Tapp et al., 2004). As in all affected species, there is substantial variation in age-associated changes among animals of comparable age in addition, controlled comparative studies of the development and composition of lesions in different breeds of dogs are lacking. The age-related cognitive decline in aged dogs can be ameliorated by a diet rich in antioxidants and mitochondrial co-factors, as well as by behavioral enrichment (Milgram et al., 2005 Siwak et al., 2005), and there is evidence that drugs used to treat cognitive decline in humans can be usefully tested in aged canines (Studzinski et al., 2005).

Root and tuberous vegetables

Potato tubers (Solanum tuberosum), sweet potatoes (Ipomoea batatas), carrots (Daucus carota) and red beets (Beta vulgaris L.) all contain antioxidant substances, but they are very different types of chemicals. Potatoes contain ascorbic acid and are characterised by high levels of conjugated hydroxycinnamates, Homogenised potatoes and sweet potatoes only exhibited medium ORAC compared with, for example, kale, garlic, spinach and onions.79 Ethanolic extracts of whole potatoes have been demonstrated to reduce oxidising DPPH radicals and to inhibit linoleic acid oxidation in suspension.85 More concentrated extracts of potato peels efficiently retarded carotene bleaching coupled to linoleic acid oxidation,84 and slowed the oxidation of soybean oil (active oxygen method).86 By 1964 hot water extracts of potato peels had been demonstrated to exert weak antioxidant activity in retarding development of thiobarbituric acid reactive substances when added to beef slices and in slowing the...

Cruciferous vegetables

Broccoli (Brassica olearacea L. cv Italica L.), Brussels sprouts (B. olearacea L. Gemmifera), red cabbage (B. olearacea L. cv Rubra), white cabbage (B. olearacea L. cv Alba) and cauliflower (B. olearacea L. cv Botrytis) have been reported to show significant antioxidant properties against lipid peroxidation.97 Phenolic compounds such as flavonols and hydroxycinnamic acids in the cruciferous vegetables may be responsible for the antioxidant activity rather than the main bioactive compounds in cruficers, namely glucosinolates.98,99 According to Plumb et al.78 purified glucosinolates exhibited only weak antioxidant properties and thus are unlikely to account for the antioxidant effects of extracts from cruciferous vegetables. Compared to other vegetables and cauliflower, kale (B. olearacea L. cv Acephala), Brussels sprouts and broccoli were found to exert higher antioxi-dant activity.70,80,97,100 White cabbage was reported to show more than 80 inhibition of coupled oxidation of...

Sources of further information and advice

As interest in functional foods and other products with possible health effects is escalating a large number of industrial enterprises are now producing various 'antioxidant' concentrates. Industrial enterprises range from the traditional juice producers and large companies specialising in natural flavours and colours to new companies specialising in health promoting supplements. There is a sparcity of published knowledge available on the molecular composition and the proven health effects of most of these antioxidant concentrates, but many of them are nevertheless claimed and marketed as having potential physiological benefits, or at least to 'supply high amounts of antioxidants'. Some caution in the evaluation of these advertisements is recommended. At the time of writing, the precise action mechanisms of antioxidants and their individual and combined efficiency have not been elucidated in detail. Thus, despite our rather detailed understanding of the various mechanisms by which...

Dietary strategies to prevent the development of heart disease

Most investigators agree that atherosclerosis is a chronic low-grade inflammation disease.29 Pro-inflammatory factors (free radicals produced by cigarette smoking, hyperhomocysteinaemia, diabetes, peroxidised lipids, hypertension, elevated and modified blood lipids) contribute to injure the vascular endothelium, which results in alterations of its antiatherosclerotic and antithrombotic properties. This is thought to be a major step in the initiation and formation of arterial fibrostenotic lesions.29 From a clinical point of view, however, an essential distinction should be made between unstable, lipid-rich and leucocyte-rich lesions and stable, acellular fibrotic lesions poor in lipids, as the propensity of these two types of lesion to rupture into the lumen of the artery, whatever the degree of stenosis and lumen obstruction, is totally different. The oxidised LDL theory is not inconsistent with the well-established lipid-lowering treatment of CHD, as there is a positive correlation...

Introduction role of processed fruits and vegetables in the modern diet

Vegetable products, including tomatoes, contain many substances which may have beneficial effects on health, providing protection from certain pathologies correlated to oxidative processes. These substances have differing functions, such as free radical scavengers, singlet oxygen quenchers, metal chelants and inhibitors of enzymes involved in the formation of the active species of oxygen.3 Epidemiological studies have demonstrated that tomato consumption provides a protective effect against some types of cancers and ischaemic heart diseases. This protective effect has mainly been ascribed to the antioxidant activity of some tomato components. rich in one of them lycopene. Tomato is the main dietary source of lycopene, the typically red-coloured carotenoid. Othercarotenoids,such as b-, g-and Z-carotene, lutein, phytoene and phytofluene, are also present, though in much lower concentrations, with vitamin C, andvitaminEintheseeds.4 Moreover, there is a growing interest in other...

Superoxide Dismutases and Catalases

Recently, SOD has been shown to protect beer against free radical damage (92). Obviously, the commercial feasibility of SOD as an antioxidant depends on cost, particularly compared to chemical antioxidants, if permitted. As far as is known, SOD is not used commercially as an antioxidant in food systems.

Nutritional quality of processed tomato

Today, the consumer faces new socio-economic and therefore food factors which tend to favour service (or convenience) quality. A service which, first of all, meets the requirements of new life systems but which also takes into account the renewed attention to hygienic and dietary aspects of food i.e. its nutritional quality, particularly in the light of the supposed antioxidant activities of some microcom-ponents, particularly lycopene. Tomato products are important foods from a sensory point of view, with good service quality and positive effects towards the prevention of the most important and common diseases of the modern world.

The late response to injury

An interesting avenue of research is into bacterial translocation and the development of sepsis. Glutamine enteral nutrition has been shown to decrease this phenomenon, but isolation of specific protein involved in bacterial translocation, and their antagonism, may be possible future therapeutic options. In the future, care of the severely injured patient is likely to undergo some exciting changes, with the emergence of combination antioxidant therapy, activated protein-C trials, and blood substitutes, which may improve outcome and ultimately survival.

Risk Factors and Neurocognition

Numerous lifestyle factors that promote or reduce risk for chronic disease have known a impact on cognitive function and its decline. Various health-compromising behaviors exert a negative influence on cognitive function, whereas health-enhancing behaviors are associated with higher levels of performance or potential improvement with intervention. Lifestyle factors can influence cognitive performance by impacting the brain directly or by promoting or reducing the development of chronic diseases that in turn affect the brain. Examples of health-compromising behaviors that are associated with lower levels of cognitive function include smoking (Swan and Lessov-Schlaggar, 2007), heavy alcohol consumption (Oscar-Berman and Marinkovic, 2007), dietary insufficiencies (Gillette et al, 2007), and physical inactivity (Colcombe et al, 2004). Health-enhancing behaviors such as greater intake of antioxidants including omega-3 fatty acids, and vitamins C and E have been associated with higher...

Innate Immune Responses Friend or

Most studies consider the induction of innate immune responses such as cytokines, chemokines, oxidative stress, and proteases to be detrimental to the neuron. This concept has been applied to most neurodegenerative diseases, including HIV-associated cognitive impairment (Fig. 1). However there are reasons to believe that in the setting of viral infections, such responses may not always be hostile to the host. Organisms that lack a cellular immune response often use such innate immune responses to protect themselves from invading pathogens. For example, plants, without a specific adaptive immune system, may use metalloproteinases, along with other innate defense mechanisms, to combat infection. For example, the metallo-proteinases-2 gene of the soybean, Glycine max, is upregulated in response to a variety of infections (1). Thus in circumstances where the cellular immune responses fail to control the pathogen such as persistent HIV infection of the CNS, the innate immune responses get...

Introduction oxidative stress and cardiovascular disease

This chapter will focus on the potential roles of fat-soluble nutrients and fat-soluble antioxidants in preventing cardiovascular disease (CVD). Two fat-soluble vitamins will be discussed in detail, i.e. vitamin E and vitamin D. Vitamin E (tocopherols and tocotrienols) is generally considered an antioxidant nutrient, although it may have important functions unrelated to its antioxidant functions (as discussed below). Antioxidant nutrients function by preventing damage to biological systems caused by reactive oxygen species (ROS) and or reactive nitrogen oxide species (RNOS). Vitamin D (calciferols) is not a true vitamin since it is not required in our diet, can be produced in skin tissue, and is generally not present in plants. Vitamin D is, perhaps, best described as a steroid hormone precursor. Although vitamin D may function as a membrane antioxidant under in vitro conditions (Wiseman, 1993), its primary biological role is to maintain plasma calcium and phosphorus homeostasis. The...

The Relevance Prion Protein Function And Copper Binding To Prion Disease

Recently studies of transition metals in prion diseases have begun to emerge. Studies of the brain of CJD patients have shown that the levels of copper in their brains are decreased (81) (Fig. 6). Similar studies with mice experimentally infected with the disease scrapie confirm this result. The changes in copper in this model precede neruonal death and follow the course of PrPSc generation in the brain. Furthermore, analysis of PrPSc isolated from the brain of CJD patients and mice with scrapie has shown that this protein lacks significant copper binding and the antioxidant activity associated with PrPC has been lost completely. This implies that prion disease does cause a loss of PrPC function that is directly related to the ability of the protein to bind copper. Maintaining functional PrPC is clearly advantageous and there is evidence to suggest this can protect against prion disease (Fig. 7). PrP knockout mice that have been modified to express hamster PrP via a GFAP promoter...

Bioavailability of lycopene

As long as lycopene remains in the aqueous matrix and more so if it remains inside the undamaged cells it is very stable but has little reactivity. Its bioavail-ability is therefore small and its efficacy as antioxidant almost zero. In contrast, its high solubility in a lipid medium (for instance in certain products formulated with oil) imparts considerable reactivity as well as complete bioavailability. Its assimilation is decidedly better if foods are cooked and homogenised so as to disrupt the cells and even more so if this occurs in the presence of oils or fats. However this effect is inevitably counteracted by a more rapid degradation of its antioxidant power. When lycopene solubilises in a lipophilic matrix, it has considerable reactivity and more availability, thus enabling it to undertake its antioxidant activity. However, this greater reactivity also means that it is more unprotected against the degradation effects of environmental conditions (air, biological matrix...

Alternative mechanisms for foam cell formation

An alternative mechanism for LDL macrophage uptake (and foam cell formation) that does not require prior formation of oxLDL is provided by mast cells. Mast cell degranulation produces neutral proteases, such as chymase, and granules. The released granules bind LDL and this LDL is also degraded and fused by the released proteases. In vivo evidence suggests that these non-oxidative modifications of LDL promote its phagocytosis by macrophages leading to foam cell formation in the human arterial intima (Kovanen, 1996). Although antioxidants certainly inhibit oxidative modifications to LDL they may also prevent atherosclerosis by inhibiting mast cell degranulation. It is known that mast cell degranulation and histamine release is stimulated by membrane lipid peroxidation and inhibited by antioxidants such as alpha-tocopherol (Masini et al., 1990). Mannaioni and Masini (1988) have provided an excellent review of the evidence linking histamine release with the generation of free radicals....

The Genotoxic Mechanism

Free radicals are reactive atoms with unpaired electrons. Radicals of the oxygen and nitrogen species are known to oxidize DNA and induce damage. Oxidative damage is associated with inflammation, neurodegenerative diseases, aging, and cancer (41-43). Acute and large amount of oxidative damage are cytotoxic to the cells and chronic low level of damage may interfere with cell cycle control (44). Estrogen-induced tumor estrogen and its metabolites are known to induce mammary tumors in rodents and humans, pituitary tumors in rats, and kidney tumors in hamsters. Estrogen is metabolized by cytochrome P450 enzymes mostly in the mammary gland and uterus, which forms hydroxylated metabolites. Chemicals that alter estrogen metabolism (such as benzo(a)pyrene, dimethylbenz(a)an-thracene) are known to induce DNA synthesis, decrease apoptosis, and enhance cell proliferation (81). At least two mechanisms have been proposed, and they are not mutually exclusive. One...

Cristina Magi Galluzzi and Angelo M De Marzo Introduction

Etiologic factors associated with PCA are varied and comprise both genetic and environmental influences. Among the genetic factors aging, family clustering, race, and hormonal influences seem to play a major role. A diet high in animal fat and red meat and poor in fruits and vegetables, and the preventive use of antioxidants associated with a high intake oftomatoes are also critical factors (3,4).

Vitamin E and measures of cardiovascular function

Despite the mixed results when the outcome measures are myocardial infarction or stroke, there is considerable evidence that vitamin E has a positive effect on other measures of cardiovascular function. For example, a study by Skyrme-Jones et al. (2000) found that 1000 IU of vitamin E (all-racemic alpha-tocopherol) for 3 months improved endothelial function and blood flow in patients with type I diabetes and reduced the oxidative susceptibility of LDL. This study had an excellent study design, i.e. double-blind, placebo-controlled, and randomized. The relationship of oxidative stress to diabetes and the potential use of antioxidants is an area of intensive research (Laight et al., 2000). Owing to an epidemic of childhood obesity, the incidence of type II diabetes is expected to dramatically increase in the near future.

Age Dependent Ultrastructural Changes in Insect Tissues

As mentioned above, adult insects are composed of nondividing (postmitotic) cells. Tissue degeneration with advancing age resembles that of brain and other postmitotic tissues in mammals. The observed changes in dipterans like Drosophila or Musca, however, are not uniform, ranging from ''total degeneration'' to ''poorly developed changes.'' We use Panorpa as a model organism not only for comparative reasons but also because, as said above, this insect shows senescent tissue degeneration even under free-living conditions (Collatz and Collatz, 1981). Figure 21.3 shows an example of tissue degeneration in senescent Panorpa. It should be possible in such an organism to demonstrate protective effects of various drugs (e.g., antioxidants) on tissue degeneration.

Metabolic Aging Studies

All metabolic aging studies on substrate and enzymatic level can profit by the basic similarity of the insect metabolism with that of other organisms, including man. It is therefore not surprising that many studies deal with enzyme activity or substrate changes in aging insects. Their antioxidative system garnered more attention with increasing knowledge of the role of free radicals and oxidative stress in aging and disease. Before showing some examples of such measurements, it seems advantageous to give some technical comments for the work with insects like Phormia.

Examples Of Metabolic Determinations

The thiole glutathione (GSH) is the most important nonenzymatic antioxidant in organisms and exists in considerably high concentrations in all cell types. GSH can react with electrophilic compounds or free radicals. The content of GSH in aging tissues generally declines, and it is assumed that this decline reduces the capacity to defend toxic effects of free radicals. Buthionin sulfoximine (BSO) is an irreversible inhibitor of the y-glutamylcystein synthetase, which is a key enzyme for the synthesis of GSH. BSO can be used to empty the intracellular stores of GSH. This allows conclusions about the protective role of GSH.

Basic Principles And Concepts Of Mechanismbased Sar In Predicting Carcinogenicity Of Chemicals

Except for some direct-acting carcinogens, most chemical carcinogens require metabolic activation to electrophilic species that bind covalently with nucleophilic sites in DNA to initiate carcinogenesis. The metabolic activation of chemical carcinogens by various metabolic systems has been reviewed (4). Table 1 lists examples of electrophilic species that are possible or probable ultimate carcinogens of a variety of chemical carcinogens. Some of the commonly encountered electrophiles or electrophilic intermediates in these chemical carcinogens include carbonium ions (alkyl-, aryl-, benzylic), nitrenium and aziridin-ium ions, epoxides and oxonium ions, episulfonium ions, aldehydes, polarized double bonds (a,P-unsaturated carbonyls or carboxylates), peroxides, free radicals, acylating intermediates, quinone and quinoid intermediates. The structural Carbon-centered free radicals or radical cations

Bactericidal activity and bacteriostasis mechanisms of action

Molecular oxygen is relatively inert but can react with organic molecules, inducing the production of highly reactive intermediates free radicals or reactive oxygen species (ROS)2930. The development and accumulation of free radicals account for the bactericidal and bacteriostatic effects of an increase in pressure of oxygen. It is generally agreed that bacteria with no defence mechanisms against free radicals are more susceptible to an increase in pressure of oxygen5,16. Free radicals are a type of molecule with one or more free electrons. Oxygen molecules include two free electrons on two different orbitals but spinning in parallel. To react with other molecules and accept electrons (oxidation), these must spin inversely - this is why molecular oxygen is not very reactive. But when oxygen molecules accept just one electron, an oxygen superoxide radical (O2 ) is formed30 with many molecules such as DNA, proteins and carbohydrates. It also destroys membrane lipids in a lipid...

Suceptibility of bacteria to oxygen mechanisms of defence

The oxygen tolerance of bacteria is related to their defence mechanisms against free radicals superoxide dismutase, catalase, glutathione peroxidase and NADH oxidase being the main enzymes involved5,30. Superoxide Dismutase (SOD) is bacterial main defence against free radicals. This enzyme catalyses the dismutation reaction which eliminates the superoxide and turns it into hydrogen peroxide which is less toxic 2O2 + 2H+ H2O2 + O2 All SODs are metalloproteins. MnSOD (manganese SOD) is located in the mitochondria, whereas Cu & ZnSOD (copper and zinc SOD) is present in the cytoplasm. These destroy the free radicals produced in the cells where they are located because generally O2* does not pass through biological membranes. There is also a extracellular form of Cu & ZnSOD5,30. Hydrogen peroxide (H2O2) is eliminated by the enzymes catalase and glutathione peroxidase - the latter requiring reduced glutathione and selenium. These induce the breakdown of hydrogen peroxide into water and...

Dean Filandrinos Thomas R Yentsch and Katie L Meyers

John's wort has demonstrated clinical efficacy for mild to moderate depression and compares favorably to other more potent or toxic antidepressants. Low side effects and potential benefits warrant its use as a first-line agent for select patients with mild to moderate depression or anxiety-related conditions. Benefits related to other reported uses such as an antimicrobial, agent to treat neuropathic pain, antiinflammatory, treatment alternative for atopic dermatitis, and antioxidant are either not well documented or evidence is encouraging but not conclusive and further study is needed. St. John's wort has an inherently wide margin of safety when taken by itself, with most reported adverse drug reactions (ADRs) being related to skin reactions. Isolated, but more significant ADRs have been reported in relation to neurological effects, impact on thyroid function, and increased prothrombin time. Of greatest concern is the potential for interactions between St. John's wort and...

Consequences of hypoxia on polymorphonuclear microbicidal activity

In vitro and in vivo experimental research has largely demonstrated the deleterious effects of hypoxia on phagocytosis. In 1976, Hohn compared the bactericidal activity of cultures of Staphylococcus aureus exposed to pressures of oxygen ranging from 0 to 150 mmHg in the presence of normal human polymorphonuclear leukocytes (PMN's) and PMN's from children suffering of Chronic Granulomatous Disease (CGD)40. They observed that bactericidal activity in normal PMN's decreased when oxygen pressure dropped under 30 mmHg and this was only half the normal activity in pressures around 0 mmHg, reaching a level similar to that of CGD subjects (Figure 1.6-1). However, the decrease in bactericidal activity of the hypoxic PMN's was reversible when normal conditions of oxygenation were restored in the environment, while those of PMN's of CGD subjects were not. Hypoxia, which is the equivalent of a lack of substrate in terms of the oxidative burst phenomenon, has similar consequences to those of the...

Stress Resistance And Extended Longevity

As a result of our studies on the biochemistry and stress resistance properties of the long-lived La strains, we knew that the only predictive factor clearly and significantly associated with extended longevity in our strains was an enhanced resistance to oxidative stress (Arking et al., 1991 Force et al., 1995). Thus it seemed logical to conclude that the long-lived La animals probably live long because of higher-than-normal activity of the antioxidant defense system genes early in life. Quantitative trait loci (QTL) mapping is a genetic method of identifying small chromosome regions which have a significant statistical effect on longevity, and may be viewed as a genome-wide scan that allows one to identify interesting genes for further investigation. Curtsinger and Khazaeli (2002) did such a procedure on recombinant inbred strains derived from the La and Ra strains discussed above. They found four QTLs located on chromosomes 2 and 3 of the (La x Ra) recombinant inbred strains that...

Physiologic Effects Of Hyperbaric Oxygen On Ischemiareperfusion Phenomenon

Abstract Reperfusion injury is a complex but clinically well-defined entity although its complete mechanism is not entirely elucidated yet. The re-oxygenation phase is characterized by vasoconstriction, platelet and polymorphonuclear leukocytes activation, and release of mediators and the production of free radicals. The goals of the available therapeutic approaches are to oppose directly the consequences of re-oxygenation following the ischemic phase. Clinical and research evidence demonstrated that hyperbaric oxygen could be effective to reduce or stop ischemia-reperfusion related injury. Although many unanswered questions remain and the effects of hyperbaric oxygen seem paradoxical at first glance, the supportive literature is growing Keywords hyperbaric oxygen ischemia-reperfusion free radicals hypoxia no-reflow oxygen paradox

How Do Different Pathways Yield a Common Type I Phenotype

The interesting thing about the Type 1 phenotype is that delaying the onset of senescence means that the inflection point characteristic of such survival and mortality curves is shifted to some later time (see Figures 25.1A, 25.2A). What happens at that inflection point, regardless of its chronological value, that shifts the population from a state of health into a state of senescence Senescence is the stochastic and nonpro-grammed loss of function which becomes obvious as the reproductive period ends. This is a time-independent process, occurring at about two years in a mouse but at about fifty-five years in a human. What triggers its onset In the fly, it has been shown that the repression of the ISP results in the activation of the dFOXO gene, and in the activation or repression of a whole suite of downstream genes under its singular or joint control (Murphy et al., 2003). These downstream genes include a variety of stress resistance genes, including a number of molecular chaperones...

Calcium and ischemiareperfusion

Calcium metabolism is affected by ischemia-reperfusion syndromes but the entire mechanism of this perturbation needs to be clarified15. Almost the entire intra-cellular calcium concentration is bound to phospholipids or proteins, or sequestered into the endoplasmatic reticulum, to calciosomes and mitochondria. In physiologic conditions, a very large electrochemical driving force tends to translocate calcium into cells. This force has two components (1) a chemical gradient - intra-cellular calcium concentration being 104 lower than the extra-cellular concentration - and (2) an electrical gradient - the electrical potential across plasma membranes (the inside being 60-90 mV negative to the outside). It is clear that a coupling exists between influx of calcium into the cells and their production of reactive oxygen species. Mitochondrial calcium accumulation and oxidative stress can trigger the assembly of a high-conductance pore (i.e., MPT or mitochondrial permeability transition) in the...

CoQIO in heart disease

Although ubiquinol may inhibit the formation of oxidized and atherogenic forms of LDL, it is likely that the primary mechanism whereby CoQ10 could prevent heart disease is through its ability to improve ATP synthesis in cells with a high ATP demand such as cardiac myocytes. As an antioxidant, ubiquinol could also inhibit the free radical damage to the myocardium that arises during ischemia-reperfusion injury. Heart failure (due to cardiomyopathy and congestive heart failure), as discussed above, is a major and increasing worldwide health problem. It is logical to suggest that dietary CoQ10 supplementation could increase ATP production and thereby improve myocardial contractility. A meta-analysis of eight randomized controlled studies looking at the effect of dietary CoQ10 supplementation on congestive heart failure indicates an improvement in stoke volume, ejection fraction, cardiac output, cardiac index, and end diastolic volume index (Soja and Mortensen, 1997). These results...

Annual Fish as a Tool for Screening for Antiaging Drugs

In 1999, we suggested that zebrafish could be used as a model for drug discovery (Jagadeeswaran et al., 1999). Due to the availability of a large number of chemical compounds and the ease of screening the larvae, a number of mutants are being investigated to reverse the phenotype with these chemicals. Such reversal of phenotypes has been applied to aortic coarctation (Peterson et al., 2004). This phenotypic reversal is feasible because the larvae are small and it is possible to accommodate screening in a 96-well format in tiny volumes such that only small amounts of chemical are used. However, in longevity studies such screening depends on the availability of compounds on a large scale and continuous replacement of the chemicals to accommodate for their half-lives. Interestingly, there are several naturally occurring compounds that are either antioxidants or participate in metabolic pathways that affect aging. Thus, in the future, it is anticipated that large-scale screens could be...

Biological Distribution Of

The study by Godin and Ganett (25) showed that the distribution of GPX in mammalian tissues is strictly functionally related to other antioxidant enzymes such as superoxide dismutase (SOD EC 1.15.1.1) and catalase (EC 1.11.1.6). It should be kept in mind that the level of GPX is subject to numerous influences, including dietary selenium, age and sex, and estrous cycle, and other environmental factors (26-28).It has been documented that GPX activity is subject to large species differences in all organs (20).

Role of leukocytes during ischemiareperfusion

Ischemic hypoxia induces an inflammatory reaction and activates polymorphonuclear leukocytes (PMN's) by pro-inflammatory mediators. PMN's then adhere to the micro-vascular endothelium by means of adhesion molecules, a process mediated largely via CD11a CD18 and CD11b CD18 interactions with intercellular adhesion molecule-1. PMN's are required for necrotic debris removal after severe ischemia. The cascade of diapedesis is orchestered by these adhesion molecules (selectins, integrins), cytokines and NO. The ensuing tissue damage is no longer limited to free radicals but also by proteolytic enzymes released by PMN's (elastases, collagenases, gelatinases) activated by HOCl. Importantly, proteolytic enzymes demonstrate a much longer activity than free radicals, partially explained by the neutralization effect of free radicals on the anti-proteases shield.

Methods In Enzymology

Oxygen Radicals in Biological Systems (Part B Oxygen Radicals and Antioxidants) Volume 299. Oxidants and Antioxidants (Part A) Edited by Lester Packer Volume 300. Oxidants and Antioxidants (Part B) Edited by Lester Packer Volume 301. Nitric Oxide Biological and Antioxidant Activities (Part C) Edited by Lester Packer

Pharmacological Toxicological Effects 51 Immunological Effects

One constituent of Echinacea, the polysaccharide arabinogalactan, has been identified as a macrophage activator in vitro, causing macrophages to attack tumor cells and microorganisms. When injected into mice intraperito-neally, arabinogalactan was able to activate macrophages. Macrophage production of tumor necrosis factor (TNF)-a, interleukin (IL)-1, and interferon-B2 was increased in vitro, and production of oxygen free radicals was increased both in vitro and in vivo (6). 5.8. Antioxidant Effects

Risk factors for coronary heart disease CHD the role of oxidative stress

Different stage in a chronic inflammatory process in the artery. The lesions of atherosclerosis represent a series of highly specific cellular and molecular responses that can be described as an inflammatory disease. Possible causes of endothelial dysfunction leading to atherosclerosis include hypercholesterol-aemia, hypertension, diabetes mellitus, cigarette smoking, elevated plasma homocysteine concentrations, infectious microrganisms and ageing. Framingham's studies have shown how each factor and combination of these factors are associated with atherosclerotic diseases.9 All these factors can be associated with oxidative stress.10-15 The beneficial effect of alpha-tocopherol and ascorbic acid is mediated by their antioxidant actions in preventing atherosclerosis. On the other hand, the effect of alpha-tocopherol could also be mediated by its antiplatelet and anti-coagulant actions, which would prevent the thrombotic consequences of atherosclerosis.16'17 Cigarette smoking,...

Salicylate 1monooxygenase EC 114131

This reaction has been found to occur non-enzymatically in rat, catalysed by free radicals formed by the parkinsonism-inducing ion MPP + J681 . In rat liver the formation of catechol and other products from salicylate is catalysed by the action of hydroxyl free radicals rather than by the direct action of a decarboxylating hydroxylase J754 .

The Detection Of Oxidative Stress

Lipid peroxides are the products of chemical damage done by oxygen free radicals to the polyunsaturated fatty acids of cell membranes, which can be measured with an assay of total thiobarbituric acid-reactive substances (TBARS) in serum using HPLC18,20. The HPLC separation step isolates the TBARS from potential interfering compounds that can give false elevations in a simple colorimetric assay. The results provide a measure of total serum lipid peroxidation, an indicator of whole body free radical activity.

Protection Against Hboinduced Dna Damage

Consequently, the effect of the interaction between HBO, NO, and HO-1 on DNA damage was investigated in rats exposed to hyperbaric oxygen39. Increased NO formation due to pretreatment with the NO-donor SIN-10 doubled the HBO-induced DNA single strand breaks. Furthermore, the increased DNA damage affiliated with HO-1 blockade seemed to be independent of endogenous NO production, since blood nitrite and nitrate concentrations, a surrogate for NO production, remained unchanged during HO-1 inhibition. The latter result suggests that the protective effect of HO-1 is related to the formation antioxidant molecules generated by HO-1, e.g. the heme degradation products bilirubin and iron, rather than the regulatory function of HO-1 with respect to NO production.

Pathogenic Mechanisms in Friedreich Ataxia

Altered iron metabolism, free-radical damage, and mitochondrial dysfunction all occur in FA patients, suggesting that information derived from investigations on frataxin function and from the yeast and animal models is relevant for the pathogenesis of the human disease. Oxidative stress is revealed by increased plasma levels of malondialdheyde, a lipid peroxidation product (Emond et al. 2000), increased urinary 8-hydroxy-2'-deoxyguanosine, a marker of oxidative DNA damage (Schulz et al. 2000), decreased plasmafree glutathione (Piemonte et al. 2001) and elevated plasma glutathione S-transferase activity (Tozzi et al. 2002). Increased free-radical production could be directly demonstrated in cultured cells engineered to produce reduced levels of frataxin (Santos et al. 2001). In addition, H2O2 induces apop-tosis in patients' fibroblasts at lower doses than in control fibroblasts (Wong et al. 1999), suggesting that even nonaffected cells are at risk for oxidative stress as a consequence...

Cellular Copper Homeostasis

Another copper chaperone, Atxl (antioxidant 1), was first identified as a suppressor of oxidative damage in yeast cells lacking SOD1 (29). Atxl is a 73-amino-acid cytosolic polypeptide with a singe amino terminal MTCXXC copper-binding motif. Atxl binds one Cu(I) atom per polypeptide involving the thiol ligands of the two cysteines (30). The Cu-Atxl complex is proposed to move to the trans-Golgi network (TGN) where it interacts with the N-terminal MTCXXC residues of the yeast Menkes ortholog Ccc2 protein and copper is transferred by a series of two- or three-coordinate Cu-bridged

Perspectives for Treatment

Additional ways to treat the disease may become apparent from studies on the function of frataxin. On the basis of these findings, therapeutic approaches aimed at controlling the levels of free radicals and regulating respiratory chain activation may be proposed. Concerning antioxidant molecules and respiratory chain stimulants, some coenzyme Q derivatives (idebenone, CoQ-10) have already yielded promising results, not only in experimental models (Seznec et al. 2004), but also in clinical trials, at least with respect to FA cardiomyopathy (Buyse et al. 2003 Mariotti et al. 2003). Automated high-throughput tests to evaluate a large number of molecules for their ability to correct the functional consequences of frataxin deficiency are under way. An intriguing possibility would be the identification of small molecules capable of effectively replacing frataxin by binding mitochondrial iron and increasing its bioavailability.

Bcl2 and related genes in the regulation of apoptosis

This is supposed to be the result of deregulation of the bcl-2 Ig fusion gene. But T-cell lymphomas which do not show this translocation do express bcl-2 protein (Pezzella et al., 1990 Kondo et al., 1992), albeit at a lower level than Bcell lymphomas (Zutter et al., 1991). Therefore, there might be other mechanisms by which bcl-2 expression is deregulated. Two bcl-2 proteins, bcl-2a and bcl-2 , produced by mRNA splicing have been identified (Seto et al., 1988). The bcl-2 protein is associated with the inner and outer mitochondrial membranes (Hockenbery et al., 1990 Monaghan et al., 1992 Nakai et al., 1993 Nguyen et al., 1993a Lithgow et al., 1994). However, apoptosis can occur in human mutant cell lines that lack mitochondrial DNA and can be protected from apoptosis by an over-expression of bcl-2 protein. Apoptosis also occurs in anucleated cytoplasts and is prevented by bcl-2 overexpression (Jacobson et al., 1993, 1994). This suggests that the bcl-2 protein may occur at...

Micronutrients Alleviating Nutritional Disorders By Nutraceuticals

In adults, superoxide, hydrogen peroxide, and hydroxy radicals (produced by some 1010 free radicals per cell each day) can potentially cause in the order of 106 mutational alterations of DNA per cell per day. Fortunately, the activities of these dangerous mutagens are countered by antioxidants, DNA repair, the removal of persistent alterations by apoptosis (normally a cellular program is activated, that causes the cell to self destruct), differentiation, necrosis, and activation of the immune system so that only about one mutation per cell per day persists (13). By old age, many mutations have accumulated because the repair system is not working properly, and as a consequence, cancer may occur. However, the increased consumption of dietary antioxidants such as vitamins C and E, quercetin (flavonoid), and carotenoids (zeaxanthin and lycopene) can diminish DNA oxidation and therefore, less cancer incidence is presented (3,13-18).

Conclusion and future trends reconciling the evidence

On the basis of these considerations we can conclude that there is compelling evidence that enhanced oxidative stress is detectable in patients with classic risk factors for atherosclerosis, but its impact in the context of atherosclerosis, progression is still unclear. The reason for this uncertainty is due to the lack of clear evidence indicating that markers of oxidative stress, such as blood lipid peroxides or urinary F2-isoprostane, are of some value for predicting the progression of atherosclerosis, even if there is some evidence suggesting that antibodies against oxidized LDL may be of some utility.67 Conversely epidemiological studies seem to indicate that low antioxidant status increases the risk of cardiovascular disease. Clinical characteristics of patients with low antioxidant status have not been defined and should be studied in the near future. So far, clinical trials with antioxidants included patients without evaluating either oxidative stress or antioxidant status and...

Cardiovascular Complications

Cardiac late effects are most closely associated with the anthracycline class of chemotherapeutic agents (doxorubicin, mitoxantrone, epirubicin). One of the mechanisms by which these drugs work is the creation of free radicals which damage the DNA of replicating cancer cells. However, free radicals also damage normal tissue. Cardiac muscle is particularly vulnerable because it lacks sufficient glutathione, which neutralizes free radicals. As a result, cardiac muscle accumulates progressive damage with increasing exposure to anthracycline drugs resulting in cardiomyopa-thy and congestive heart failure. This may also lead to arrhythmias. Consequently, the anthracycline class of chemotherapeutic agents each has limits above which exposure is not considered safe for example, 450 mg m2 for doxorubicin and 900 mg m2 for epirubicin. Several drugs commonly combined with anthracyclines in breast cancer, such as cyclophosphamide, paclitaxel, and herceptin also have cardiac toxicity, thereby...

Aging Research on Bats

A more recent study tested the free radical theory of aging (Harman, 1956) as an explanation for the extreme longevity of bats. In a comparative study, Brunet-Rossinni (2004) measured mitochondrial hydrogen peroxide production in heart, kidney and brain tissue of the little brown bat, Myotis lucifugus, the short-tailed shrew, Blarina brevicauda, and the white-footed mouse, Pero-myscus leucopus. Hydrogen peroxide production per unit of oxygen consumed was significantly lower in the bat tissues than in the two nonflying mammals. Brunet-Rossinni also measured activity of superoxide dismutase, a key enzyme in the antioxidant defense system of mammalian tissues. Activity of this enzyme did not differ between the three species. Though not an all-inclusive assessment of antioxidant defenses, this study suggests that free radical production is a better predictor of bat longevity than metabolic rate and antioxidant activity. Similar results have been found in birds and other mammals (Herrero...

Leslie Helou and Ha M Harris

Garlic possesses a variety of beneficial pharmacological properties affecting most notably the cardiovascular system (lipid management, decreased blood pressure, platelet inhibition, and decreased fibrinolytic activity), and the immune system as an antineoplastic and immunostimulant agent. It is also a potent antioxidant. Although its effects are modest in some clinical applications, its inherent safety and culinary benefits usually support its use when a mild clinical effect is acceptable. There is the potential for interactions with drugs possessing antiplatelet and anticoagulant effects. Additionally, potential induction of various cytochrome P450 enzymes warrants closer monitoring of drugs metabolized through this pathway when garlic is concomitantly administered. Key Words Allium sativum antilipemic platelet inhibition antioxidants cancer prevention P450 enzyme induction.

Pharmacological Toxicological Effects 51 Cardiovascular Effects

Antioxidant and Antiatherosclerotic Effects Garlic has been shown to have significant effects on the cardiovascular system. Such areas include improvement in lipids, modest effects on blood pressure, platelet inhibition, antioxidant effects, and a decrease in fibrinolytic activity. In vitro studies have shown garlic possesses specific antiatherosclerotic effects such as reducing inducible nitric oxide synthase (iNOS) mRNA expression (10), inhibition of oxidized low-density lipopro-tein (LDL)-induced lactate dehydrogenase (LDH) release and inhibition of oxidized LDL-induced depletion of glutathione (11). The effects of garlic as an antioxidant and its ability to alter the atherosclerotic process require additional study. To date, no trials evaluating patient outcomes have been completed.

Vitamins and nutraceuticals

The term carotenoids summarizes a class of structurally related compounds, which are mainly found in plants, algae, and several lower organisms, bacteria, and fungi. At present, more than 600 different carotenoids have been identified (72). Saffron, pepper, leaves, and red palm oil possessing carotenoids as their main color components, have been exploited as food colors for several centuries. The color of carotenoids, together with beneficial properties such as vitamin A precursor and antioxidant activity, has led to their wide application in the food industry. They have been used for pigmentation of margarine, butter, fruit juices and

Iiimportance To Quality Of Food

LOX is known to have several detrimental effects in foods (see reviews 36, 37), and these effects can be controlled by various methods of enzyme denatura-tion. By the process of cooxidation by free radicals, LOX activity is known to cause bleaching of carote-noids, chlorophyll (38, 39, and Refs. therein), and oxidation of ascorbic acid (40). LOX probably accounts for a large portion of pigment bleaching and loss of quality observed in unblanched frozen vegetables. In addition, products of LOX action, fatty acid hydroperoxides, are cleaved both enzymically and nonenzymi-cally into odorous shorter-chain aldehydes, alcohols, and alkanes. The nonenzymic formation of odors is very detrimental leading to complex free radical products broadly defined as rancidity (see review 41). LOX reactions can even occur in dry substrates at the lowest relative humidities examined (52 ) (42). It was also demonstrated that LOX action in dry substrates initiated free radical autoxidation of...

Properties As Enzyme A Specific Mechanism of Action

Although many inhibitors of LOX have been investigated, only representative examples can be cited here. First, it should be emphasized that soybean LOX catalyzes its own destruction during oxidation of substrate. The destruction is greater with substrates of a higher degree of unsaturation (86). Several types of inhibitors mainly can be categorized as follows (for citations also see 86 and Refs. therein) (a) substrate suicide inhibitors, such as acetylenic fatty acids (irreversible) (87) (b) chain-breaking antioxidants (usually competitive and reversible) (88) (c) iron chelators (often reversible) (89) (d) disrupters of the active site (90) (e) reductants of the active-site iron (91) (f) free radical reactions with LOX, such as with hydroxyl radicals produced from H2O2 (presumably irreversible)

An Experimentally Induced Decrease In Oxidative Stress Retards Ageassociated Deterioration At The Organelle And

Reducing dietary intake has been shown to be the most effective means for modulating the aging processes in laboratory rodents (Weindruch et al., 1986). Dietary restriction also has been shown to be a modulator of membrane lipid peroxidation and cytosolic antioxidant status. Lee et al. studied the anti-ROS action of dietary restriction by quantifying the formation of the O2* OH , and H2O2 by liver microsomes from rats of various ages. The results show that the ad libitum-fed group maintained a higher production of O2*_ and OH radicals when compared to the food-restricted group of the same age. H2O2 formation followed the same trend but was statistically greater only at three and six months of age. The food-restricted group displayed higher SOD activity in both cytosolic and mitochondrial fractions compared to ad libitum-fed controls (Lee and Yu, 1990). These data indicate that the ROS activity observed in liver microsomes of ad libitum-fed rats can be attenuated by dietary...

Consumption of soybean and reduced incidence of disease

Phenolic compounds normally occur as glucoside bound moieties called glycones (22,23). However, it is the aglycone (glucoside free) form that is metabolically active (24). After consumption, probiotic enzymes in the intestine cleave the glycoside moieties from glycone isoflavonoids and release the biologically active health-promoting aglycone isoflavonoids. Aglycone phenolic compounds possess higher antioxidant activity and are absorbed faster in the intestines than glucoside bound forms (23,25,26). Interestingly, fermented soy foods are rich in phenolic aglycones due to microbial bioprocessing during fermentation (27,28). However, once inside the bloodstream, biologically active aglycone genistein travels to the liver were it is converted back into an inactive glycone (b-glucuronide) (24). Cellular glucuronidases must remove the glycone moiety before genistein can exert its biological activity (24). Isoflavonoids have been well studied and possess numerous biological activities (1)....

Experimental Evidence that Is not Readily Explained by the Mitochondrial Theory of Aging

H2O2 formation are much lower (less than 0.1 of respiratory chain electron flux). This H2O2 production may be stimulated by the complex III inhibitor antimycin A, but not by myxothiazol (Hansford et al., 1997). Staniek and Nohl further reported that mitochondria respiring on complex I and complex II substrates generate detectable H2O2 only in the presence of the antimycin A. They also suggested that the rates of mitochondrial H2O2 production reported by others are artificially high due to flaws in experimental design (Staniek and Nohl, 2000). Martin Brand's group capitalized on these findings and used an improved experimental design to show that mitochondria do not release measurable amounts of superoxide or hydrogen peroxide when respiring on complex I or complex II substrates, but release significant amounts of superoxide from complex I when respiring on palmitoyl carnitine (St-Pierre et al., 2002). However, even at saturating concentrations of palmitoyl carnitine, in their...

Measuring The Changes In The Levels Of Dna Repair Enzymes

Earlier we mentioned the lack of consensus regarding the age-related trend in mitochondrial content of DNA-repair enzymes, with some groups reporting an increase and others reporting a decrease. Both increase and decrease in the activity of DNA-repair enzymes in mitochondria appear to be consistent with increased oxidative stress and an increased number of oxidative mtDNA lesions with aging, phenomena on which a consensus does exist. Therefore, decreased expression of DNA repair enzymes is believed to result in a decreased ability of mitochondria to repair oxidative lesions, which leads to their accumulation. On the other hand, increased expression of DNA repair enzymes was interpreted to represent an adaptive response to increased oxidative stress. The magnitude of this response is believed to be insufficient to completely protect mtDNA when oxidative stress overwhelms antioxidant and DNA-repair systems, resulting in the net accumulation of oxidative DNA lesions. This ambiguity in...

Action of the soybean isoflavone genistein

The mechanistic coupling of mitochondrial ATP generation and oxPPP through proline metabolism that supports normal cells during stress and which appears to be dysfunctional in many tumorigenic cells provides a foundation for a possible model mechanism for the chemopreventive action of phenolic antioxidants, such as genistein, against certain cancers (100). Once activated by glucuronidase, free genistein may stimulate proline metabolism through the activation of proline dehydrogenase (PDH) via p53. Genistein can induce p53 expression in colorectal cancer cells (124). The mechanism for stimulation of p53 by genistein is not clear, but other dietary antioxidants can activate p53 by a refl dependent redox mechanism (125,126). The transcription factor p53 can activate PDH, as well as ROS and apoptosis in cancer cells (127-129). Stimulation of mitochondrial PDH in the tumor cell by phenolic antioxidants such as genistein should cause a demand for proline (117) that would have several major...

Pathogenic mechanisms of ironinduced atherosclerosis

As a redox active metal, iron is capable of catalysing the formation of hydroxyl radicals in the Fenton reaction (Marx & van Asbeck 1996). Several antioxidants have been shown to protect against the endothelial dysfunction associated with atherosclerosis (Diaz et al. 1997). The oxygen radicals may involve in the regulation of nuclear factor KB (NF-k ) DNA binding (Baldwin 2001), important for the transcription of a large number of genes, including the endothelial adhesion molecules (Collins et al. 1995 Neish et al. 1992).

Measuring iron toxicity

In the early course of iron overload, numerous homeostatic mechanisms prevent damage from accumulating iron. These include increased ferritin production needed to sequester the labile iron, and increment in individual antioxidants and or antioxidant enzymes to protect against radical damage promoted by iron. However, these mechanisms might fail as more iron accumulates.

Biological Function of Phenolic Phytochemicals

Compelling epidemiological and scientific evidence has led to an understanding that oxidative stress, as a consequence of an imbalance of prooxidants and antioxidants, is a key phenomenon in the manifestation of chronic diseases (90). Powerful strategies to control oxidative stress related pathogenicities are gaining prominence. Epidemiological evidence showing that populations consuming diets rich in fruits and vegetables have lower incidences of many chronic diseases such as cancer, cardiovascular diseases and diabetes has led to an interest in the use of diet as a potential tool for the control of these oxidative diseases (86-89). Recent in vitro and clinical studies have shown that diets rich in carbohydrates and fats induced oxidative stress, which was decreased by consuming fruits, vegetables, and their products (93). Among all the dietary components, fruits and vegetables have especially been shown to exert a protective effect (23-26). Phenolic phytochemicals with antioxidant...

Solidstate bioprocessing

Fermented foods have been consumed by humans all over the world for centuries. Most fermentation processes are conducted with liquid nutrient broths. Well known examples in the food industry are the production of yogurt, beer, wine, lactic acid, and many food flavors (213). However, partial fermentation and aerobic microbial growth based bioprocessing has also been used for processing food and food wastes. Here, instead of a nutrient broth, moist solid nutrients with minimal water are used as a substrate for microbial growth. This process is referred to as solid-state bioprocessing. Microbial fermentation and aerobic microbial growth on foods in solid state, for preservation of food and flavor enhancement, has been done for centuries and some of the common examples for these processes include manufacture of cheese and bread (214). Other wellknown examples are the production of microbe laced cheeses such as Roquefort, and the production of fermented sausages. In Asia, solidstate...

Interaction Of Factors

Sorbic acid at 1000ppm and pH 7.0 will not inhibit mold growth. However, if the pH is lowered to 5.0, growth of most molds will be inhibited (Liewen and Marth 1985). Antioxidants such as BHA and BHT have been shown to potentiate the action of sorbic acid (Scott 1989). In general, antifungal food additives become more effective as environmental conditions move away from the optimum for a particular organism.

Validity of Accelerated Aging Phenotypes

Interestingly, the single-gene mutations that increase life span in worms, flies and mice may do so through the upregulation of cellular defense systems, including DNA repair and antioxidant defense. Candidate genes implicated in the control of such a survival response are FOXO and SIRT1, which have been demonstrated in nematodes and fruit flies to control downstream targets of the pro-longevity mutations affecting nutrient sensing, reproduction, and growth (Vijg and Suh, 2005). Down-regulation of these effector genes could then conceivably lead to an acceleration of all possible aging phenotypes. FOXO3a and SIRT1 knockout mice do not display apparent signs of accelerated aging, although it is possible that a progeroid phenotype will become visible after a more quantitative downregulation of these genes (Cheng et al., 2003 Hosaka et al., 2004).