Natural Powerful Antioxidants

Vitamins and Minerals as Antioxidants

Several vitamins and minerals are considered antioxidants. These include vitamins E and C, beta-carotene (which can be converted to vitamin A), other carotenoids (some may be converted to vitamin A and also play a role in cell devel opment), and the minerals selenium, copper, zinc, and manganese. What are antioxidants What do they do Every cell in our body needs oxygen to use the nutrients that food provides. However, when oxygen is used by cells, by-products called free radicals are formed. If allowed to accumulate, these free radicals can damage tissues, cells, and deoxyribonucleic acid (DNA, the genetic material of cells). The process of oxidative damage can be observed as the browning that occurs when sliced apples or potatoes are exposed to the air or the rancid flavor that butter and cooking oils develop when stored for long periods. Environmental pollutants such as cigarette smoke and ultraviolet light from the sun also contribute to the formation of free radicals in our...

Enhancement of Cellular Antioxidant Detoxification Capacity

Oxidative stress and the inflammatory microenvironment of the tissue act as predisposing factors to multistage carcinogenesis 1,11,12 . Reactive oxygen species (ROS), such as superoxide anion, hydroperoxyl radical, hydrogen peroxide, and hydroxyl radical, are constantly generated in cells as unwanted by-products of aerobic metabolism. Although a low physiologic level of ROS is scavenged efficiently by the cellular antioxidant defense system, an imbalance between the generation of ROS and cellular antioxidant capacity turns into a state of oxidative stress that contributes to carcinogenesis 13-15 . Oxidative stress contributes to Detoxifying Antioxidants Enzymes (e.g., HO-1, SOD NQO1, etc.) Detoxifying Antioxidants Enzymes (e.g., HO-1, SOD NQO1, etc.)

What are the Cellular Effects of the Non Antioxidant Properties of the Tocopherols

The mechanism by which vitamin E produces cellular events could be in principle related to the known radical chain breaking properties of the molecule. This would imply that regulation of certain cellular functions is controlled by the production and elimination of lipid soluble free radicals and that vitamin E serves as a radical scavenger. The biological difficulty of controlling the propagation of radical chain reactions makes this mechanism improbable. Furthermore, if this were the mechanism of action of the tocopherols, other similar radical chain braking molecules, and in particular the eight natural tocopherol analogues, would act analogously this is however often not the case. Thus, it can be assumed that a-tocopherol modulates cellular behavior by specific interactions with enzymes, structural proteins, lipids and transcription factors. Similarly, troglitazone, an antidiabetic drug of the thiazolidinedione class, acts as an insulin sensitizer and improves hyperglycemia....

Oxidative Stress Antioxidants And Lipid Peroxidation

A weakening of antioxidant defenses has been convincingly demonstrated in both human diabetic patients and experimentally diabetic rodents, although there appear to be tissue-dependent differences (cf. van Dam 1995 Low et al. 1999 for references). In several non-neural tissues, GSH concentrations as well as Cu-Zn superoxide dismutase and catalase activities are decreased in diabetes. In the case of the peripheral nerve, information is relatively scant, but as compared to the brain and liver, the activities of free-radical scavenging enzymes, except for superoxide dismutase, in the normal tissue are markedly lower (Low et al. 1999). In experimental diabetic neuropathy, Cu-Zn superoxide dismutase activity is substantially reduced, whereas reports conflict regarding changes in glutathione peroxidase (Low and Nickander 1991 Hermenegildo et al. 1993 Kishi et al. 2000). GSH is also decreased in diabetic nerve, whereas catalase activity is enhanced (Nickander et al. 1994 Nagamatsu et al....

Antioxidant Properties Of Inositol Phosphates In Vitro

Phytate is a very stable and potent chelating agent that exhibits the ability to complex a variety of divalent and trivalent ions. At physiological pH, InsP6 forms complexes with Cu2+, Zn2+, Co2+, Mn2+, Fe2+, and Ca2+ 3 . Because phytate binds essential minerals and can prevent their absorption, most human nutritionists view the compound negatively. However, its unique chelating action with iron provides phytate with antioxidant characteristics. In the iron-assisted Haber-Weiss reaction, the formation of OH requires the availability of at least one reactive iron coordination site, as well as iron solubility. Evidence that all six phosphates on myoinositol are not required for the inhibition of hydroxyl radical formation was presented by Hawkins et al. 6 . They showed that Ins(1,2,3,4,6)P5 and DL-Ins(1,2,3,4,5)P5 were effective at inhibiting hydroxyl radical formation to a greater degree than Ins(1,3,4,5,6)P5 and DL-Ins(1,2,4,5,6)P5 and concluded that the 1,2,3-trisphosphate grouping...

Antioxidant Properties Of Inositol Phosphates In Vivo

A question that remains is whether this antioxidant property of phytate might function in vivo, and whether it mediates the potential disease-sparing characteristics of phytate that have been observed in cancer studies 10 . To test this hypothesis, researchers have used cells in culture or animal models and measured the ability of phytate to attenuate the oxidative stress induced by various means. To date, the literature on this question is equivocal, with some studies indicating that InsP6 provides some antioxidant protection, whereas other studies have found no effect or a pro-oxidant effect. It is important to recognize that oxidative stress protection in biological systems is a complex and multifaceted process 11,12 , thus the ability of phytate to contribute as an antioxidant in vivo may only be evident under conditions in which stress is invoked. In contrast to the previously discussed studies in which some evidence of antioxidant function in vivo was presented, other studies...

Phytate As An Antioxidant In Chicken And Beef

Graf and coworkers 2,12 were the first to evaluate phytate as an antioxidant in a meat system. In cooked, minced chicken breast muscle +10 added water, phytic acid (1.5 mM, pH 6.0) was highly effective in reducing thiobarbituric acid (TBA) values (Figure 12.1) and warmed-over flavor (WOF) intensity (Figure 12.2), compared to controls 12 . Phytic acid (2 mM) was more effective than other antioxidants (2 mM ascorbic acid, BHT, or EDTA) for lowering TBA values in fresh beef homogenates incubated for 60 min at 37 C 13 .

Antioxidant Properties Of Wild Rice In Cooked Meat Products

A cheaper alternative to phytate is the addition of high-phytate grains to cooked ground meats. Textured soy proteins (TSP) or textured vegetable proteins (TVP) are economical extenders of ground beef patties 31 . Lower thio-barbituric acid (TBA) values were reported for ground beef patties extended with TSP 32 , indicating possible antioxidant effects during storage. Addis and coworkers 3,33-35 at the University of Minnesota demonstrated the feasibility and acceptability of wild rice addition to ground beef patties and pork sausage 36 . In addition to a lowering ofTBA values with the addition of wild rice (Table 12.5), panel evaluations indicated an actual preference for beef patties with 15 or 30 cooked wild rice, compared to all beef controls 33 . Whole-grain wild rice was a more effective antioxidant in ground beef patties than ground wild rice 3 . The antioxidant properties of wild rice kernels were due to the presence of phytic acid 34 , as indicated by the identical HPLC...

Oxidative Stress and Antioxidant Responses

There is substantial evidence that oxidative damage in the brain increases in normal aging, that it is greater in persons with AD, and greatest in the brain regions that are most vulnerable in AD, but the source of the oxidative stress resulting in these changes has been elusive (50,231,364). Regions of the brain that degenerate in AD (e.g., cerebral cortices) have been found to have a significant increase of aluminum and iron compared with age-matched controls (421). (See also ref. 251.) Surprisingly, redox-active iron has been found to be reversibly associated with the plaques and tangles of the AD brain (364). This iron may be a source of oxidative stress if there are not adequate levels of iron-binding proteins or antioxidants in the vicinity, since ferrous iron will catalyze the production of damaging hydroxyl or peroxyhydroxyl radicals in the presence of reactive oxygen species. High levels of RNA and protein for the inducible enzyme heme oxygenase-1 also are associated with AD...

Activities found in In Vitro and animal models 31 Antioxidant and antiradical activity

Antioxidant or reduction activity of calcium dobesilate is a result of its hydroquinone structure. This was mentioned above in section 2.3 in relationship to its analytical behaviour (compare Fig. 8) but this type of reactivity has also an important impact to its biological activity. The ability of 2,5-dihydroxybenzenesulfonic acid salts to reduce mercurous and silver nitrates to metallic mercury and silver respectively was first observed by Seyda (Seyda, 1883). Calcium dobesilate was shown to actively interact with toxic superoxide anion radical O2 -.This reactive oxygen species (ROS) was generated either by UV irradiation of an aqueous solution of glycyltryptohphan at 280 nm, or by irradiation of a mixture of glycyltryptophan with riboflavine with visible light. Thus calcium dobesilate showed the activity similar to that of superoxide dismutase (Lozovskaia et al., 1990). This result was confirmed in the experiment in which superoxide radicals were generated in the system xanthine...

Aging Exercise and Antioxidant Defense System

The oxidant antioxidant balance is an important determinant of immune cell function, including maintaining integrity and functionality of membrane lipids, cellular proteins, nucleic acids, and for control of signal transduction and gene expression in immune cells. Enzymatic and nonenzymatic antioxidants play a vital role in protecting tissues from excessive oxidative damage during exercise. Antioxidant enzymes play an important role in defending the cells against free-radical-mediated oxidative damage. In rats, hepatic and myocardial antioxidant enzymes are declined at older age, whereas activity of glu-tathione-related enzymes in the liver and mitochondrial enzymes in the heart are increased significantly. Skeletal muscle antioxidant enzymes are uniformly elevated during aging. The generation of oxygen free radicals and other reactive oxygen species may be the underlying mechanism for exercise-induced oxidative damage, but a causal relationship remains to be established. Depletion of...

Antioxidant Systems During Aging

Mammalian cells are equipped with both enzymatic and non-enzymatic antioxidant defense systems to cope with oxygen free radicals. Enzymatic systems are localized in all cellular compartments and include Cu, Zn-superoxide dismutase, Mn-superoxide dismutase, cata-lase, glutathione peroxidases and reductases, and peroxiredoxins 1,20,21 . Non-enzymatic antioxidant systems are small molecular weight compounds such as a-tocopherol, ascorbic acid, p-carotene, coenzyme Q (CoQ) and reduced glutathione (GSH) 1,22,23 . However, there is now growing evidence that the activity of certain antioxidants declines with age, exacerbating oxidative stress conditions 24-26 , leading to an imbalance in the pro-oxidant antioxidant ratio and accumulation of oxidative damage. The age-related decrease in the capacity of cells and organisms to respond to oxidative stress can explain their higher sensitivity to external stress such as radiation and heat shock 27 . It was shown that the difference in...

Antioxidants

The main action of antioxidants in human health is realized through their free-radical scavenging and chain breaking features. Oxygen is a potentially toxic element for living systems since it can be transformed by metabolic processes into more reactive forms such as superoxide, hydrogen peroxide, singlet oxygen and hydroxyl radicals, collectively known as active oxygen. In living cells, an enzyme called superoxide dis-mutase converts superoxide into H2O2. Hydrogen peroxide is able to cross all biological membranes. Excessive production of oxygen radicals, particularly hydroxyl radicals can cause lipid cell membranes to reduce lipid peroxides. The hydroxyl radical is very reactive as it combines with almost all molecules found in living cells. Formation of the hydroxyl radical from active oxygen requires catalysis by metal ions, e.g. iron and the copper. The ability of the copper H2O2 system to do severe damage to proteins and DNA is well established. Lipid peroxidation finally leads...

Free Radicals

Free radicals are compounds characterized by having an unpaired electron. They are in general highly reactive species, particularly those involving elements of the second row of the periodic table like O, N, C, etc. by the drive to form another chemical bond and complete the valence shell. Because a normal chemical bond consists of two electrons and two electrons only, radicals cannot react covalently with nucleophiles or two-electron species they can only react with other radicals or they can abstract a hydrogen atom from a neutral molecule to generate a new radical or abstract an electron to form an anion and generate a radical cation. While neutral, they can be considered to be electron deficient, but from the perspective that the addition of another electron to form the anion or the reaction with another radical to form a chemical bond satisfies the rule of eight and completes the second quantum level. For example, they can be deactivated by abstracting an electron from vitamin E...

Antioxidant effect

According to the Panel on Dietary Antioxidants and Related Compounds of the Food and Nutrition Board, an antioxidant may be defined as a substance that reduces significantly the adverse effects of free radicals over normal physiological function (22). Vitamin C (or L-ascorbic acid) is called electron donnor antioxidant due to its hability to prevent oxidation of other compounds by linking to their electrons (23). While ascorbic acid is oxidized in a stable and non-reactive form, free radicals are reduced to water and do not cause cellular lesion any longer (23).

Brain and Adaptive Response to Exercise Induced Oxidative Stress

Similar data have also been obtained in the rat model. A causative link has been suggested between the oxidative damage of proteins in the brain and its function. We have shown that exercise can reduce the carbonyl group content in the brain, increase the activity of protea-some and enhance memory 36 . In addition, it appears that exercise decreases the size of lesions caused by artificial stroke, and improves the regeneration of oxidative damage 18 . Neurotrophins, such as brain- derived neurtrophic factor (BDNF), play an important role in learning, memory, feeding, locomotion, stress response, neuroplasticity, neurite outgrowth, and synaptic function, for example 20 . Aging is associated with decreased levels of BDNF in the brain, and loss of cognitive function. Several lines of information suggest that voluntary and forced exercise increase BDNF content and memory 22,26 . Recently we have observed that regular exercise protects against brain deterioration, induced by a NMDA lesion,...

Role of Oxidative Stress in Aging of the Yeast Saccharomyces cerevisiae

Oxidative stress is a factor in both replicative and chronologic aging. Yeast deficient in antioxidant and antioxidant enzymes show decreased replicative and chronologic lifespan while overexpression of some antioxidant proteins prolongs the lifespan. The yeast system seems ideal to test the free radical theory of aging since it is easy to obtain yeast strains deficient in, or overexpressing, antioxidants. Moreover, S. cerevisiae, as a facultative aerobe, can be grown under aerobic, hypoxic and anoxic conditions. One could expect that, if ROS play a significant role in yeast aging, cells grown under hypoxic atmosphere should have increased lifespan and anoxia should have a dramatic life-prolonging effect. Such an effect is not observed on the contrary, a decreased replicative lifespan is observed under anoxia 7,12 . However, mutants lacking CuZnSOD or MnSOD or both have decreased replicative lifespan 7,64,65 while divergent results have been published concerning the effect of catalase...

Lipid Peroxidation Measurements Methodological Approaches and Clinical Importance

Oxygen free radicals are implicated in many diseases and ormal processes, such as ische-mia-reperfusion injury (see myocardial infarction, and stroke), cataracta, age-related macula degeneration, cancer, inflammation, aging, diabetes, and neurodegenerative diseases. For the evaluation of oxidative stress in these diseases reliable methods of assessment would be useful. If one wants to evaluate the degree or the consequences of oxidative stress one could measure the degree of protein oxidation, lipid oxidation, or nucleic acid oxidation. One group of representative parameters of oxidative stress is supplied by parameters of lipid peroxidation (LPO). Even one may think protein oxidation and nucleic acid oxidation are more important in comparison with LPO, that may be a hasty and false conclusion. Why A lot of proteins and peptides play a role which is not more important than that of lipids, such as steroid hormones, retinoic acids, prostaglandins etc. Additionally, LPO products such as...

The Msr System A Key to Longevity

The interesting possibility that the methionine sulfoxide reductases system may play a role in longevity was tested by Stadtman and Hoshi's laboratories using knock-out mice and transgenic Drosophila, respectively 69,82 . Their results suggest that overexpression of MsrA is important in death retardation. Overexpression of MsrA extended the lifespan of Drosophila by up to 70 . In wild-type Drosophila, neurons contain a high ROS production rate and endogenous Msr activity is low, implying that the latter may be a limiting factor in lifespan determination. In contrast, mice lacking the MsrA gene showed an accumulation of oxidized proteins and had a 40 shorter lifespan. A similar decrease in survival rates was observed for a MsrA null mutant of E. coli and S. cerevisiae 79,83 . In contrast, the MsrB null mutant and MsrB overexpression yeasts had only a slight effect upon lifespan. However, it was shown that the MsrA MsrB double null mutant had a lifespan which was more strongly reduced...

ROSInduced Oscillations of Mitochondrial Transmembrane Potential in Cultured Rat Astocytes

Mitochondria are not only the source but also the target for free radical damage. There is a number of data regarding permeability transition pore (PTP) induction in the cells incubated with free radicals donating substances 1-3 . At the same time experiments with isolated mitochondria show that reactive oxygen species (ROS) could also participate in PTP induction 4,5 . Both approaches have some drawbacks. In case of working with a cell culture treated with a free radicals donor the latter could affect mitochondria indirectly by activation of some metabolic cascades induced by the oxidative stress. Isolated mitochondria are deprived of their native surround and the data obtained using this model could not reflect adequately the situation taking place in an intact cell. To avoid these drawbacks Zorov and co-workers developed a model in which ROS are generated directly inside mitochondria in the living cell 6 . In this model free radicals are generated in the mitochondria...

What are the Cellular Effects of the Different Chemical Properties of the Tocopherols

Antioxidant Effects The antioxidant effects of vitamin E have been the subject of a number of reviews 6,86-92 . However, more recently interest is being developed around the novel concept that the to-copherols are provided with more and more specific non-antioxidant functions. The following paragraphs give detailed illustrations of the non-antioxidant functions of vitamin E. Although vitamin E has been described in numerous publications to act as an antioxidant, it has also been shown that lipid peroxidation of LDL is faster in the presence of a-tocopherol, and is substantially accelerated by enrichment of LDL in vitamin E, either in vitro or in vivo 93,94 . It was thus proposed that peroxidation is propagated within lipoprotein particles by the vitamin E radical (i.e. a-tocopheroxyl radical) unless it became reduced by vitamin C or ubiquinol-10 95 . However, it is not clear whether the pro-oxidation reactions of a-tocopherol are relevant in vivo, under physiological conditions....

The Oxidative Degradation of pCarotene and the Formation of Potential Toxic Degradation Products

It was already mentioned above, that p-carotene and further carotenoids not only underlie enzymatic transitions, but also non-enzymatic oxidative degradation. In every moment if a carotenoid-molecule successfully acted as an antioxidant, a carotenoid degradation product was formed. Due to many antioxidative actions of carotenoids, a high number of degradation products will be formed. It was already mentioned that one group of the primary degradation products are apo-carotenals 22-30 . Hurst investigated the degradation of carotenoids at heat and in presence of intensive cigarette smoke 37 . Without any doubt many of the degradation products are carbonyls and epoxides, which are highly reactive towards biological material 26,29,32,38 . Handelman described first the formation of oxidative p-carotene degradation products in presence of hypochlorite 25 . This condition of oxida-tive carotenoid breakdown is similar to carotenoid breakdown in inflammatory regions of the organism. Our...

The Msr System and Oxidative Stress

In a recent study, we showed that when WI-38 fibroblasts were exposed to low concentrations of H202, a mild oxidative stress treatment, MsrA and MsrB2 genes were up-regulated, suggesting that these genes are necessary for oxidative stress defense 75 . The Msr system has been described as an antioxidant system that can function catalytically since, in proteins, surface-exposed methionine residues can act as scavengers of a variety of oxi-dants 76 . In fact, it has been proposed that not all methionine residues in proteins exhibit the same susceptibility to oxidation. This susceptibility to oxidation is correlated with the surface exposure of the residue. Indeed, oxidized methionine residues were found to be relatively surface-exposed, whereas intact residues were generally buried within the core of the protein. Thus, the exposed methionine residues could act as a protective barrier for buried residues for which oxidation may become critical for enzymatic activity 76,77 . Thus, cyclic...

Methionine Oxidation and the Msr System in Aging

Methionine sulfoxide accumulation may therefore be due to a decrease in the efficacy of the Msr protein repair system. Petropoulos et al. 61 have shown, by analyzing MsrA gene expression, that MsrA is downregulated with age in rat kidney and liver, two organs considered to have detoxifying and house-keeping roles. In contrast, in the brain, the differences in gene expression were not statistically significant and the MsrA protein level was reduced only in 26-month-old rats at the very end of their lives. Using replicative senescence as a model of cellular aging, we investigated the role and regulation of the peptide methionine sulfoxide reductase system in young and old WI-38 fibroblasts 75 . We showed a reduction in Msr activity in senescent cells, correlated with a decrease in gene expression of MsrA and MsrB2 (CBS-1) proteins. This decline in MsrA and MsrB expression was associated with accumulation of oxidized proteins, as demonstrated by protein carbonyl content measurement....

Exercise Induced Adaptation

Adaptation of a biological system to particular stimuli (stress) is one of the basic homeo-static responses, which results in increased resistance to the given stimulus. Although adaptation to a stimulus is a necessary physiological function, adaptive responses to acute and repeated stimuli are very different. The stress-adaptation theory was developed for an acute stress, which takes place without interruption 43 . A single bout of physical exercise produces an adaptive response, albeit limited. On the other hand, the beneficial effects of exercise (increased muscle mass, improved cardiovascular system, decreased incidence of a number of diseases, etc.) are mostly due to the adaptive responses to regular physical exercise. It has been shown that regular physical exercise increases the generation of RONS, which could be necessary initiators of adaptive responses of the antioxidant and oxidative damage repair systems. The effectiveness of the protection repair systems can be judged by...

Functions of CEHC Metabolites

A- and y-CEHC, with their intact chroman heads or redox active moieties, have been shown to retain antioxidant activity as they can scavenge peroxyl radicals and peroxynitrite in vitro 44,45 . This may explain, in part, the protective effect seen for y-CEHC at high concentration (25 M) against metal-induced nephrotoxicity in the rat 46 .

Significance of the aTocopherol Salvage Pathway

Vitamin E is present in plants in 8 different forms with essentially equal antioxidant potential (a-, P-, y-, S-tocopherol tocotrienols) nevertheless, in higher organisms only a-tocopherol is preferentially retained suggesting a specific evolutionary reason for the selective uptake of this analogue. In the last 20 years, the route of the tocopherols from the diet into the body has been clarified and the proteins involved in the uptake and selective retention of a-tocopherol discovered. Cellular functions of the tocopherols that are independent of their antioxidant radical scavenging abilities have been characterized in recent years. Vitamin E inhibits protein kinase C (PKC), protein kinase B (PKB), tyrosine kinases, 5-lipoxygenase and phospholipase A2 and activates protein phosphatase 2A, and diacylglycerol kinase. A growing number of genes are modulated by the tocopherols at the transcriptional level. The tocopherols also inhibit cell proliferation, platelet aggregation,...

How is Vitamin E Taken up and Distributed in the Body

Apparently, the plasma and tissue levels of the four tocopherols reached by chylomicron transport is not sufficient, since a specific salvage pathway recycles a-tocopherol from the liver back into the body and mutation of this pathway leads to vitamin E deficiency syndromes (Fig. 1A). It can be speculated that the evolutionary benefit of selecting a-tocopherol for recycling by the salvage pathway did not originate only from the limited dietary availability of vitamin E or its antioxidant function for a mere antioxidant function all four tocopherols and tocotrienols could have been selected, suggesting other non-antioxidant reasons for the selection of a-tocopherol.

Biological Activities of Carotenoids and Vitamin A in

Carotenoids are efficient quenchers of singlet oxygen and can directly scavenge free radicals. Vitamin A, in contrast, is a relatively poor antioxidant. Another biological function of carotenoids in vivo is the inhibition of lipid peroxidation. This was shown in many tissues. Carotinoids also contribute to antioxi dative protection in LDL. In animal models anticarcinogenic activities were found. Possibly the anticarcinogenic activities are related to the influence of carotenoids to increased gap junction communication between cells due to upregulation of connexin 43 gene, but unrelated to the antioxidant capacities 33 . Two carotenoids play a special role in the eye, especially in the retina macular pigments lutein and zeaxanthin.

Why was aTocopherol Selected in Higher Organisms

Natural vitamin E comprises 8 different forms, a-, P-, y-, and S-tocopherol and a-, P-, y-, and S-tocotrienol produced by plants alone. Tocotrienols have an unsaturated side chain, whereas tocopherols contain a phytyl tail with three chiral centres which naturally occur in the RRR configuration (Fig. 2). Although the overall antioxidant activity of these molecules are more or less similar, clear individual chemical, physical and biological effects can be distinguished at a molecular level. Bioavailability and bioequivalence of the different forms of vitamin E differ. RRR-a-Tocopherol is the most abundant form in plasma, whereas the plasma y-tocopherol level is only about 10 of that of a-tocopherol despite that a higher amount of y-tocopherol is often present in the diet. This specificity is the consequence of a selective retention of RRR-a-tocopherol in the body, or vice versa, to the metabolic degradation of the other tocopherols and their elimination. In fact, in HMC-1 mast cells,...

What are the Effects on Gene Expression by Different Tocopherols

2) a-Tocopherol may also influence gene expression by direct modulation of the activity of specific transcription factors in a non-antioxidant fashion, for example via the pregnane X receptor 79 , possibly other nuclear receptors such as the peroxisome proliferators activated receptors (PPARs), orphan nuclear receptors, or via one of three human tocopherol associated proteins, hTAPs, recently reported to modulate gene expression 17,161 . Later on, genes were found to be modulated by tocopherols independent of PKC, and specific regulatory elements were found in their promoters, but a specific transcription factor responsive only to tocopherol or a tocopherol nuclear receptor has so far not been identified. In primary cultures of quiescent stellate cells, inhibition of collagen a1(I) transactiva-tion by a-tocopherol requires only -0.44 kb of the 5' regulatory region. Transfection of stellate cells with a collagen-luciferase chimeric reporter construct allowed localization of an...

Aging and ROS Production

Aging is a multifactorial phenomenon characterized by a time-dependent decline in physiological function, which varies between different species. Several theories have been proposed to explain the aging process. The free radical theory first proposed by Harman 12 hypothesized that free radicals produced during aerobic respiration cause cumulative oxida-tive damage to proteins, lipids and DNA, resulting in aging and death. The toxicity of oxygen is partly due to overproduction of the superoxide in the different cellular compartments of eukaryotic cells and especially in mitochondria 13,14 . At least 1 of the oxygen consumed by the mitochondrial respiratory chain leads to oxygen radical production and hydrogen peroxide formation 15,16 . Moreover, several studies on both humans and animals have demonstrated an age-related failure of mitochondrial respiration and a decrease in ATP synthase activity 17-19 , suggesting an increase in ROS production. In fact, ROS produced by normal...

Supplementation of Carotenoids for Prevention and Treatment

Due to the multitude of beneficial effects of carotenoids (antioxidant, provitamin A, immunoenhancement, antimutagenic, signal transduction) and due to the epidemiological findings arguing for a high intake of carotenoids, billions of people in western countries con sume carotenoid containing supplements every day. The aim of such supplementation should be to use the protective functions of carotenoids against the development of macular degeneration, cardiovascular diseases, irradiation induced skin aging, and cancer. Even many people followed the change from the principle An apple a day keeps the doctor away in Five servings a day keep the doctor away and use at least five servings of fruit and vegetables, billions of other people and also of those using lots of fruits and vegetables additionally take supplements with p-carotene or retinol or lycopene or other carote-noids 1 . The supplements as nutraceuticals are combinations of different compounds or single compounds. It is always...

Adaptation to Exercise Induced Oxidative Stress

Exercise increases the generation of reactive oxygen and nitrogen species (RONS), and by causing adaptations could decrease the incidence of RONS-associated diseases. A single bout of exercise, depending upon intensity and duration, can cause an increase in antioxidant enzyme activity, decrease levels of thiols and antioxidant vitamins, and result in oxidative damage as a sign of incomplete adaptation. Increased levels of RONS and oxidative damage are initiators of a specific adaptive response, the stimulation of the activation of antioxidant enzymes, thiols and enhanced oxidative damage repair. Regular exercise has the capability of developing compensation to oxidative stress, resulting in overcompensation against the increased level of RONS production and oxidative damage. Regular exercise also causes adaptation of the antioxidant and repair systems, which could result in a decreased base level of oxidative damage and increased resistance to oxidative stress. In this paper...

Clinical Use of Carotenoids Antioxidative Protection versus Prooxidative Side Effects

Carotenoids are natural pigments, which are found in bacteria, algae, fungi and plants, but which are not synthesized in animals. Animals and human beings get carotenoids through food. If we think on carotenoids, we think mostly on P-carotene, lycopene, lutein, zeaxanthin, and some others. But, meanwhile 600 to 700 carotenoids were identified. About 60 of them are components of our nutrition. Almost ten percent of all carotenoids in mammals can be metabolized to retinol, which is vitamin A, and can therefore function as vitamin A precursors. Carotenoids and retinoids act as antioxidants, influence the growth of the organism, immunologi-cal functions, the visual cycle, and modulate gene expression, too. Epidemiological data have strongly linked higher levels of carotenoid intake and increased circulating and tissue concentrations of carotenoids with reduced risk for various cancers, cardiovascular disease, and other diseases, even clinical intervention trials did not find...

Background

The discovery of these metabolites provided insight to the function of a-tocopherol in vivo. Structurally, the Simon metabolites indicated that metabolism involved both the opening of the chroman nucleus and a shortening of the phytyl side chain. As the structure of the chromanol head of a-tocopherol allows it to quench radicals through the donation of hydrogen from the hydroxyl group, the detection of metabolites with an open ring structure has been taken as further proof that a-tocopherol acts as an antioxidant prior to excretion. Metabolic studies focusing on the antioxidant functions of a-tocopherol have generally given more attention to a-tocopheryl quinone, the oxidation product of a-tocopherol. a-tocopheryl quinone is derived from the reaction between a tocopheroxyl radical and a per-oxyl radical 7 and it retains an intact side chain. Supplementation with a single dose of natural, as well as SRR-a-tocopherol in rats, resulted in an elevation of plasma and tissue a-tocopheryl...

Conclusions

The results summarized in this review strongly indicate three rather new concepts regarding tocopherols and related compounds. The first is that the data discussed in this study are altogether suggestive for an in vitro gene regulatory function of the tocopherols and to-cotrienols. It is not always clear whether the observed effects are the result of changes of gene expression or may be due to other events such as changes in mRNA or protein stability. The second is that vitamin E interacts with specific proteins, and affects the activity of these proteins in a manner specific for the different tocopherol analogues. The third clear point of this survey is that no obvious correlation exists between the described regulatory functions of the tocopherols and their free radical chain interrupting properties established to take place only within a lipid phase. As a consequence it is reasonable to assume that the basis of the selective retention of a-tocopherol is found in some of the...

The 20S Proteasome

Numerous data demonstrate that the 20S core proteasome is sufficient to degrade oxidized or misfolded proteins 5,25,26,51-60 . Normal proteins carry a hydrophilic and charged surface that cannot be recognized by the hydrophobic binding domains of the proteasomal a-subunits. As a reaction to oxidative stress, 20S proteasome selectively recognizes hydro-phobic amino acid residues, which are normally shielded, and which are exposed during oxidative rearrangement of secondary and tertiary protein structure (Fig. 1). This reaction requires no ATP hydrolysis or ubiquitinylation 5,7,26,51,61-63 . On the other hand, excessive protein oxidation leads to protein aggregation, cross-linking, and or decreased solubility 25,26,52-57,65,66 . These aggregates appear to be resistant to proteasomal proteolysis (Fig. 1). Hence, proteasome plays an important key role in the overall antioxidant defenses by minimizing protein aggregation and removal of potentially toxic protein fragments 67 .

Discussion

An early event in the development of atherosclerosis is the intimal deposition of lipids, including cholesterol. This deposition arises from a combination of extra- and intra-cellular processes and has been shown, in some animal models, to be inhibited by antioxidants 37 . We have observed a specific inhibition of proliferation in vitro of smooth muscle cells by Several groups have reported that antioxidant vitamins and especially vitamin E have an important anti-atherogenic role 3-6,38 . The question posed in this study has been (1) Does hypercholesterolemia effect smooth muscle cells, at the level of protein kinase C, a key enzyme in the control of proliferation (2) Is vitamin E capable of protecting against the molecular modifications induced by hypercholesterolemia at the level of smooth muscle cells The present in vivo data of cholesterol stimulation and vitamin E inhibition of protein kinase C activity, agree with previous results both obtained in vitro 9,11,13,39,40 and in vivo...

Discharge And Home Healthcare Guidelines

ARDS is defined as noncardiogenic pulmonary edema that occurs despite low to normal pressures in the pulmonary capillaries. Many theories and hypotheses are currently under investigation. Patients with ARDS are characterized as having high-permeability pulmonary edema (HPPE) in contrast to cardiogenic pulmonary edema. In ARDS, the alveolar-capillary membrane is damaged, and both fluid and protein leak into the interstitial space and alveoli. Recent research has focused on possible mediators of the membrane damage, such as neutrophils, tumor necrosis factor (TNF), bacterial toxins, and oxygen free radicals, among others. The onset of symptoms generally occurs within 24 to 72 hours of the original injury or illness.

Plugging of spiral arteries

The reason for such a paradoxical plugging of already eroded and transformed arteries may be as follows lack of blood cells keeps the placenta and the fetus in a low oxygen environment of less than 20 mmHg in the first trimester of pregnancy. This low oxygen environment may be necessary to prevent the formation of free radicals that affect the growing fetus in this critical stage of tissue and organ development 15-17 .

Alteration in Oxidative Stress

Increases of oxidative stress by metabolic derangement has long been reported in diabetic states and proposed to cause vascular complications (44,59,63,64). In diabetic states, induction of oxidative stress could be as a result of the increased production of superoxide anion via the induction of NADPH oxidase and mitochondrial pathway decreases of superoxide clearance lipid and protein modification and the reduction of endogenous antioxidants such as ascorbic acid, vitamin E, and glutathione. that400 IU per day of vitamin E failed to show difference in cardiovascular outcomes and diabetic nephropathy (76). However, we have reported that oral vitamin E treatment at a dose as high as 1800 IU per day appears to be effective in normalizing retinal hemo-dynamic abnormalities and improving renal function in type 1 diabetic patients of short disease duration without inducing a significant changes in glycemic control (77). At this dose, vitamin E is capable of inhibiting PKC activity (74)....

Role of 5HT and Its Transporter in MDMAInduced Neurotoxicity

It can be envisioned that activation of the 5-HT transporter by MDMA renders 5-HT terminals vulnerable to further initiators of toxicity. Indeed, MDMA-induced 5-HT neurotoxicity is prevented in animals in which the 5-HT transporter is inhibited by fluoxetine (50,51). Actions of MDMA on the 5-HT transporter may be responsible for the generation of reactive oxygen species, i.e., free radicals, or for an increase in intracellular calcium concentrations (52), both of which could contribute to the process of toxicity.

Hints For Understanding Chemical Mechanisms

Hydrogen atom abstraction from a molecule has been proposed as an intermediate during the oxidation of C-H bonds by cytochromes P450. Hydrogen atom abstraction can also occur during oxidative stress when reactive oxygen-free radicals are formed. An arrow representing the movement of electrons with two barbs represents the movement of two electrons while an arrow with only one barb represents the movement of only one electron. If a bond is broken by moving two electrons in one direction, it will result in a positive charge on the tail of the arrow and a negative charge at the head of the arrow. These charges are often dissipated by the loss or gain of a proton, i.e., the loss of a proton will remove the positive charge on a molecule while gaining a proton will eliminate a negative charge on a molecule. However, if a bond is broken by a single electron leaving that bond, no charge is produced but rather free radicals are generated. This is symbolized by an arrow with a single barb...

Role of Oxidative and Bioenergetic Stress in MDMA Neurotoxicity

Increasing evidence suggests that MDMA-induced 5-HT neurotoxicity results from increased free radical formation and the subsequent induction of a state of oxidative stress. Support for a free radical hypothesis of MDMA toxicity is based on findings that (1) MDMA increases the formation of free radicals, (2) MDMA produces cellular damage that often accompanies free radical formation, and (3) free radical scavengers and or antioxidants attenuate MDMA-induced 5-HT neurotoxicity. Although free radicals are short-lived reactive species, in the presence salicylic acid, a stable adduct, that is, 2,3-dihydroxybenzoic acid (DHBA), is formed that can be quantified analytically. MDMA produces a rapid and sustained increase in the extracellular concentration of 2,3-DHBA in brain (43,51, There are several potential sources for free radicals generated by MDMA. Dopamine may undergo enzymatic or nonenzymatic oxidation to form superoxide radical and hydrogen peroxide. The importance of superoxide...

Effects over diabetic complications

A recent report showed that all alterations induced by hyperglycemia - including aldose redutase, PKC and AGEs increases - are reversed by inhibiting free radicals production induced by glucose (25). Such fact gives the possibility that, by blocking glucose induced oxidative stress, it may also be possible to prevent lesions caused by other pathways (25). Vitamin C presents a central role in antioxidant defense system and may help to mitigate oxidative stress associated to diabetic complications (22). In fact, there are reports that high dose vitamin C diets are associated to reversion of early signs of retinopathy and to normalization of capillary resistance in diabetes mellitus, confirming its antioxidant protector role in blood vessels lesion (9,26).

Understanding Oxidative Stress

In recent years, the research disciplines interested in oxidative stress have grown and enormously increased our knowledge of the importance of the cell redox status and the recognition of oxidative stress as a process with implications for many pathophysiological states. From this multi- and inter-disciplinary interest in oxidative stress emerges a concept that attests to the vast consequences of the complex and dynamic interplay of oxidants and antioxidants in cellular and tissue settings. Consequently, our view of oxidative stress is growing in scope and new future directions. Likewise, the term reactive oxygen species adopted at some stage in order to highlight nonradical oxidants such as H2O2 and O2 now fails to reflect the rich variety of other reactive species in free radical biology and medicine encompassing nitrogen-, sulfur-, oxygen-, and carbon-centered radicals. With the discovery of nitric oxide, nitrogen-centered radicals gathered momentum and have matured into an area...

Summary And Conclusion

That its preventive efficacy must be explored extensively. Despite the relative normality of the response to moderate exercise in the elderly, they have a reduced tolerance of free radicals and greater vulnerability to micro-injuries and an acute-phase response from overexertion. It might thus be anticipated that they would more easily reach the point where natural immunity is suppressed and vulnerability to infection is enhanced. Older adults may have to adopt a more cautious approach and follow a moderate exercise regimen along with a nutritionally well-balanced diet. Training in theory has a number of actions which could help to reverse the impact of aging upon the immune system, including a direct modulation of sympathetic activity in the neurohypophysis, a reduction of cross-linkages and a diminution of free-radical formation.

Hyperglycemia and glucose transporter GLUT1

Hyperglycemia (an increased blood D-glucose concentration) is the most important symptom exhibited by diabetic patients, and this has severe effects on the development of diabetic retinopathy (Cai & Boulton, 2002). At the inner BRB, the retinal endothelial cells express facilitative glucose transporter, GLUT1 that recognizes hexoses and dehydroascorbic acid (DHA) as substrates (Vera et al., 1993). GLUT1 mainly mediates the influx transport of D-glucose across the inner BRB. GLUT1 exhibits an asymmetrical localization at the inner BRB, and the abluminal expression of GLUT1 protein is 2- and 3-times higher than that on the luminal membrane (Takata K et al., 1992 Fernandes et al., 2003), suggesting that GLUT1 suppresses glucose accumulation in the retinal interstinal fluid. Regarding the influx permeability rate, the blood-to-retina transport is 544 and 2440 microL (min- g retina) for D-glucose and DHA, respectively (Puchowicz et al., 2004 Hosoya et al., 2004). DHA is the oxidized form...

Analytical strategies

An intervention study is a type of prospective study that can be very conclusive as well as very expensive. In intervention studies, the epidemiologist intervenes with the study population, e.g., smokers given a pill containing vitamin E, vitamin C, and beta-carotene to test the effect of supplemental antioxidants on the incidence of lung cancer. Thus, the investigator exerts a degree of control over the risk factors of interest, i.e., intakes of antioxidants.

Neural theories of sleep function

As originally proposed at the beginning of the twentieth century, the hypnotoxin theory of sleep function posited that sleep removes a noxious by-product of the waking brain 94 . Modern versions of this theory propose that sleep reverses or protects against neuronal damage caused by prolonged glutamate release or oxidative processes that occur during wakefulness 95-97 . For example, it is hypothesized that uridine and glutathione accumulate in the brain as a function of waking metabolism and induce sleep by enhancing GABAergic and reducing glutamatergic synaptic transmission, respectively. In addition, glutathione has potent antioxidant properties and is hypothesized to protect cells from oxidative damage 95 . While it is true that exogenous uridine and glutathione induce sleep, and both molecules accumulate in neural tissues of sleep-deprived rats 95,98 , the extent to which waking or sleep influences oxidative processes in the brain is controversial. Prolonged REM sleep deprivation...

Regulation Of Expression

Regulation of expression varies between GST classes. In the promoter, response elements to transcription factors including the antioxidant response element, xenobiotic response element, glucocorticoid response element, Barbie box element, and GSTP enhancer 1 have been identified. Motifs for YY1, AP-1, MAF, Nrfl, Jun, Fos,

Measurement Of Fatty Acid Composition

In order to identify fatty acids present in the different lipid classes, the extraction mixture chloroform methanol (2 1, v v) proposed by Folch et al. (1957) is ideal for the initial total lipid extraction process since it will extract both the neutral triacylglycerol components as well as more polar phospholipid components of the tissue without damage to the fatty acids. An antioxidant such

Competitive and Antagonistic Interactions

In this process, for example production of hydroxyl radicals by the brown-rot fungus Antrodia vaillantii increased during interaction with the bacterium Pseudomonas fluorescens (Tornberg and Olsson, 2002). Bacteria surviving in wood colonized by decay fungi must have sufficient antioxidative activity to protect themselves from being attacked by free radicals.

Strategies to improve cell productivity

Rosmarinic acid and related phenolics are natural antioxidants found as secondary metabolites in spearmint (Mentha spicata) and other plant species. These phenolic secondary metabolites have diverse food-processing and nutraceutical applications. Since natural cross-pollination results in plant-to-plant variation in the level of phenolic metabolites, tissue-culture-based techniques are essential to isolate elite antioxidant-producing clonal lines. Tissue-culture-based selection techniques to isolate high ros-marinic acid and phenolic-producing clonal lines from a heterogeneous bulk seed population of spearmint have been developed by Al-Amier and colleagues (1999).

Practical Applications

Secondary metabolites of basidiomycetes often have antimicrobial properties and are screened for their use as novel medicines (Abraham, 2001 Liu, 2005). Wood-inhabiting bacteria have, so far, not been studied in this context. Yet, they may reveal a new source of antimycotica and antioxidants.

Nutrient Composition

A medium-sized raw carrot is an excellent source of beta-carotene, which is converted into vitamin A. Carrots are a relatively good source of fiber. In addition to beta-carotene, carrots contain two other carotenoids alpha-carotene and lutein. The carotenoids, which are responsible for the bright-orange color of carrots, have antioxidant properties and may help prevent cancer and heart disease. Lutein also has been looked at for its role in protecting the eye from free-radical damage and maintaining vision. Cooking carrots makes them more digestible and appears to increase the amount of vitamin A available for use in the body. However, the vitamin A content of fresh or frozen carrots is twice that of canned versions.

Prophylactic therapies

The key to modern management of pre-eclampsia is close surveillance and timely delivery prior to serious consequences. In an ideal world preventing the manifestation of the disease would be far more preferable. Aspirin, calcium, and antioxidants have all been investigated, with some evidence of success. Fish oils, magnesium and even rhubarb 23 have shown less promise.

The Complexity of Sex Steroid Actions

The mechanism of action of both estrogens and progestogens on the vascular system is diverse and complex. Some of the estrogen actions, including those on the atherogenic lipoproteins, antioxidant activity and enhancement of endothelial function are unequivocally antiatherogenic. Some of these effects, however, may be partly negated by certain synthetic progestogens used in conventional HRT. On the other hand, the net clinical effect of the prothrombotic vs fibrinolytic actions of estrogens may vary depending on dose, route of administration, the state of the vascular wall and genetic factors, so that in certain circumstances the prothrombotic effects may predominate resulting to thrombosis.

Oxidative Stress Chemical Mechanisms

Oxidative stress is defined as a condition in which there is an imbalance between production of reactive oxygen species (ROS) in tissues or cells as a result of pro-oxidant effects and their removal by means of antioxidant defenses that scavenge free radicals. Growing evidence indicates that the presence of excessive levels of ROS is a contributory factor in the onset of diabetic complications, as it is in the pathogenesis of atherosclerosis and several neurodegenerative diseases. Abnormally high levels of ROS may be generated in diabetic tissues as a result of several mechanisms, among which are lipid peroxidation, nonenzymatic glycation of proteins, and glucose autoxidation. These processes appear to be enhanced in the presence of transition metals (Hunt and Wolff 1991 van Dam et al. 1995). The most reactive ROS are superoxide (O2-) and hydroxyl radicals, both of which are free radicals with short half-lives. Superoxide is also produced as a consequence of respiratory chain electron...

Therapeutic Approaches

A variety of compounds intended to combat oxidative stress have been used to treat experimental diabetic neuropathy and considerable success has been attained in correcting neural and vascular abnormalities (cf. Cameron and Cotter 1999). These substances include hydrophilic and lipophilic free-radical scavengers, as well as chelators of transition metals. A complete discussion of these approaches is beyond the scope of this chapter. However, it is pertinent to comment on several in the context of essential fatty acid metabolism. The effectiveness of the hydrophilic substance, -acetylcysteine, may derive either from its antioxidant properties or its ability to prevent reduction in nerve GSH content by acting as a precursor for synthesis of the tripeptide (Sagara et al. 1996). It is of interest that exposure of transformed Schwann-cell cultures to micromolar concentrations of -acetylcysteine partially prevents the depletion in ACMS (Kuruvilla and Eichberg 1998b). The lipophilic...

Sampling Extraction and Spectrophotometry

Microbial biomass, usually from the stationary phase of growth and other comparative samples (e.g., carotenoid-containing fruits and seeds) are used as dry starting materials through lyophilization. Heat application or hot-air ovens should be avoided for moisture removal because of the ease of oxidation of carotenoids. Although the dry state is not a sine qua non condition for the efficient carotenoid extraction, water is better in the next partition step of the moisture-free organosolvent extract regardless of the coapplication of an intermediate saponification step. In any instance, the conjunction of light, heat, and oxygen is very harmful to carotenoid native structure. Hence, whenever possible, a flux of nitrogen (e.g., solvent deaereation) is strongly recommended. For those carotenoids not readily available as purified standards, the above procedure may be also applied (e.g., for the preparation of canthaxanthin, astaxanthin, and apocarotenoic acid ethyl ester starting from the...

Dairy Products Cheese

Extending the shelf life and or sterilization of dairy products for immunocompromised patients using radiation treatment is not a widely accepted practice. The main reason for its limited use is that ionizing energy, through the formation of radiolytic products especially in high lipid-based foods, generates unacceptable off-odors and flavors via oxidation, polymerization, decarboxylation, and dehydration reactions even at low doses.2241 In particular, polyunsaturated fatty acids are prone to oxidation by free radicals produced during treatment. In addition, oxidation of casein and the production of methyl radicals has been shown to result in the generation of wet dog off-flavors.42 These chemical reactions, to some extent, can be reduced if the products are initially frozen and or treated in an environment with limited water, light, and oxygen. Yet, despite these shortcomings, low-dose radiation for the specific purpose of extending dairy product shelf life does hold promise. In such...

Oxidative and Nitrosative Stress in Diabetic Cardiomyopathy

There is circumstantial clinical and experimental evidence suggesting that increased sympathetic activity, activated cardiac renin-angiotensin system, myocardial ischemia functional hypoxia, and elevated circulating levels of glucose result in oxidative and nitrosative stress in cardiovascular system of diabetic animals and humans. Oxidative stress associated with an impaired antioxidant defense status may play a critical role in subcellular remodeling, calcium-handling abnormalities, and subsequent diabetic cardiomyopathy (75,89). Oxidative and nitrosative damage may be critical in the early onset of diabetic cardiomyopathy (74,75). Consistent with this idea, significant nitrotyrosine formation was reported in cardiac myocytes from myocardial biopsy samples obtained from diabetic and diabetic-hypertensive patients (74) and in a mouse model of streptozotocin (STZ)-induced diabetes (75). Perfusion of isolated hearts with high glucose caused a significant upregulation of iNOS, increased...

Reaction and Stereochemistry

Despite the fact that carbanions and free radicals play no part in the action of phospho-rylase, it is a pyridoxal-5'-phosphate (PLP) enzyme, and PLP is absolutely required for activity. The most intriguing aspects of the reaction mechanism are the role of PLP and the mechanism by which retention of anomeric configuration is brought about. Neither of these has been satisfactorily explained to the date of this writing, despite several decades of intensive study in a number of laboratories.

Prions proteinaceous infectious particles

PrPC isoform is a 33- to 35-kDa sialoglycoprotein with 208 to 220 amino acids, is expressed predominantly in the central nervous system, and is attached to the surface of neurons and other cell types by a glycophosphatidyl inositol (GPI) anchor. Two thirds of the molecule at the carboxyl terminal end is a helix bundle structure and the remaining 80 to 100 amino acids at the amino-terminal end contain a copper ion-binding motif. The normal function of PrPC may be to traffic copper ions. PrPC possesses superoxide dismutase activity and may play a role in cellular resistance to oxidative stress. Thus, the conformational shift from the helical cellular PrPC to a sheet-rich pathogenic isoform PrPSc can result in loss of Cu-mediated antioxidant function and in a microenvironment (perhaps producing a metal ion prooxidant situation) that is more conducive to oxidative stress, which can trigger a neurodegenerative cascade. Use of antioxidants in PrP-related diseases has been proposed in...

Protecting against anthracycline induced cardiac damage

However, their use is limited by a dose-dependent toxicity.18 The mechanism for this toxicity is not clear. Among possible mechanisms are the formation of toxic free radicals through mitochondrial pathways19 and direct damage to cardiac myocytes.20 Clinically, anthracycline induced cardiac toxicity is either acute, early- or late-onset. Acute toxicity, occurring immediately or during an infusion of anthracy-cline, is rare (

Components of HPLC Analysis

The column used for a specific separation is based on the type of the molecules to be analyzed. Various types of chromatographic modes can be used for the separation of the molecules. For example, ion exchange columns separate charged molecules such as amino acids, proteins, or nucleotides. Size exclusion columns separate organic polymers such as polyvinyls and silicones or biopolymers such as proteins, nucleic acids, or sugars. Adsorption columns separate molecules based on their interaction with the stationary phase. This mode is useful for the separation of vitamins, dyes, lipids, phenols, and antioxidants. Partition columns are used to separate molecules based on the way that the solvent becomes partitioned into stationary and mobile layers, and is useful in analyzing steroids, aromatics, vitamins, and antibiotics. The molecules eluting from any one of these different types of column are then analyzed by various types of detectors, measuring absorbance, fluorescence, or...

Biochemical and Physiological Effects

Here the discussion is not on biochemical causes of toxic effects, as discussed in Section 17.1, but on the secondary effects that are manifested biochemically. These are the changes in the operation of biochemical pathways that do not involve the toxin directly. They are the chemical response of the cell to toxin-induced damage to enzymes, reactants, or cell structures involved in reactions. As mentioned above, the distinction is sometimes arbitrary. For example, enzyme disruption by the complexation of metallic cofactors, or production of free radicals by oxidants, could both be considered secondary effects. Some

The Phospholipid Hypothesis

Thus far, we have reviewed evidence demonstrating that a depletion of PUFAs in RBC membranes and an over activity of PLA2 may be responsible for stripping away those PUFA. Other evidence has suggested that sufferers of schizophrenia also show increased levels of oxidative stress. Mahadik et al. (1998) reported elevated plasma lipid peroxides in first-episode nonaffective psychosis. Recently, the Scottish Schizophrenia Research Group (2000) has suggested that such findings could be an artifact caused by smoking, which, in itself, causes oxidative stress. However, work by our group (Zhang, 1999) has demonstrated increased oxidative stress in unmedicated schizophrenic patients who do not smoke. Oxidative stress could be either a cause or a consequence of increased breakdown of membrane PUFA. Yao et al. (1998) showed a reduction in plasma total antioxidant capacity in schizophrenic patients, which was not attributable to antipsychotic drug treatment. Mukerjee et al. (1996) also showed...

Oxidative Stability

An important contribution to the literature was made by Zalewski and Gaddis 101 , who investigated the effect of transesterification of lard on stability, antioxi-dant efficiency, and rancidity development. Interesterification of lard did not affect its resistance to oxidation, but changes in oxidative stability due to tocopherol decomposition and the formation of reducing substances were noted. In the absence of antioxidants, both interesterified and native lard had similar peroxide values. Furthermore, because of the position of unsaturated fatty acids at 1,3-positions or randomization toward the 2-position in pork fat triacylglycerols, there was no appreciable effect on initiation of oxidation and autoxidation rates.

Other interventions in male factor infertility

Interventions which have been shown to be ineffective include anti-oestrogens (clomifene and tamoxifen), androgens, bromocriptine and kinin enhancing drugs. Antioxidants (Vitamins C and E and glutathione) can improve semen parameters in men, but in the absence of data on more definitive outcomes such as pregnancy or live-birth rates, their use cannot yet be recommended. Mast cell blockers have shown some initial promise in men with severe oligizoospermia (National Collaborating Centre for Women's and Children's Health (NICE) guideline, 2004).

Apoptosis In Ischemic Injury

Solid evidence has been collected to indicate that the deleterious factors activated in ischemic cells are capable of initiating apoptosis. Using in vitro models, ATP depletion has been shown to activate caspases through the mitochondrial pathway, involving the translocation of Bax from cyto-sol to mitochondria followed by the release of cytochrome c from the organelles (15). Stepwise or gradient depletion of ATP upregulates Fas-Fas ligand system, triggering apoptosis through the death-receptor pathway (16). Disturbance of Ca2+ homeostasis has been proposed as a trigger for apoptosis for some time (17). Increases of cytosolic free Ca2+ have been demonstrated in apoptotic cells. Moreover, amelioration of Ca2+ increases within cells diminishes apoptosis under certain situations. Echoing these observations, pharmacologically induced increases in cytosolic Ca2+ lead to the development of apoptotic morphology in diverse types of cells. Free radicals that are produced during ischemia or...

Apoptotic Pathways In Ischemic Cell Injury

For the intrinsic pathway, mitochondrial damage characterized as interruption of respiration and development of permeability transition pores has been long recognized as a key event in ischemic cell injury (78). Cytochrome c, a central molecule relaying apoptotic signals from mitochondria, is released into cytosol in ischemic tissues (33,79-81). For example, global brain ischemia in rats leads to accumulation of cytochrome c in the cytosol of neurons in the hippocampus, which is accompanied by sequential activations of caspases-9 and -3 (81). Of interest, transgenic rats overexpressing superoxide dismutase (SOD) produced less free radicals during ischemia, and apoptotic progression was significantly suppressed (81). The results suggest an important role for oxygen free radicals in ischemic activation of the mitochondrial apoptosis pathway. Alternatively, development of mitochondrial pathology in ischemic cells might be caused by the dysregulation of Bcl-2 family proteins. A good...

Consequences Of Cuttinginduced Injury On Quality Retention

Atmospheres (2.65 O2, 3.65 CO2 at equilibrium). In fact, they found increased microbial growth in packages containing the ethylene adsorbent. This was likely due to the fact that sulfur volatiles were also removed from the package headspace by the absorbent, and it is known that some sulfur volatiles produced by injured onion tissues have antimicrobial properties (Blanchard et al., 1996). No response or improvement in quality was found with use of ethylene adsorbents in packaged, minimally processed carrot sticks (Howard and Griffin, 1993). Another issue regarding ethylene activity is that wounding induces the production of allyl isothiocyanates in cabbage, and these compounds are strong antioxidants that can suppress both wound-induced ethylene production and browning (Nagata, 1996). Therefore, accumulation of secondary metabolites may impinge on other physiological responses to cutting, depending on the product in question, and thus, must be kept in mind.

Reduction of retinal albumin leakage by calcium dobesilate

The action of calcium dobesilate on retinal albumin leakage in streptozotocin-diabetic rats was investigated together with relevant in vivo retinal antioxidant and permeability markers, i.e., carboxymethyl-lysine-advanced glycation end product (CML-AGE) formation and vascular endothelial cell growth factor (VEGF) overexpression. Twenty days after streptozotocin administration, diabetic rats were treated for 10 days with calcium dobesilate (100 mg kg day per os) or vehicle. Retinal albumin leakage, CML-AGE formation, and VEGF overexpression were evaluated by immunohistochemistry of frozen eye sections. Diabetic rats exhibited dramatic increases in retinal albumin leakage (31 of positive vessels vs. 0.2 in nondiabetic rats, CML-AGE retinal occurrence (40 3 vs. undetectable positive vessels), and retinal VEGF protein expression (14.6+1.1 vs. 3.5+0.5 VEGF-positive spots field). Calcium dobesilate significantly reduced retinal albumin leakage (by 70 ), retinal CML-AGEs contents (by 62 ),...

Type I And Type Ii Pathways Of Excited Triplet Sensitizer

The excited triplet sensitizer may interact directly with substrate such as linoleic acid or phenol compounds by donating an electron or accepting hydrogen, resulting in the production of free radicals or free radical ions as shown in Figure 5. This mechanism is known as type 1 pathway 25,26 . The photosensitizer acts as a photochem-ically activated free radical initiator. The product radicals have a variety of possible reactions, such as reaction with, or electron transfer to, oxygen and electron or hydrogen abstraction from other substrates. After initiation of the free radicals (R-), the radical compound may react with triplet oxygen via free radical oxidation mechanisms. The rate of the type 1 pathway is mostly dependent on the type and concentration of the sensitizer and substrate. Compounds that are readily oxidizable compounds, such as phenols, and easily reducible compounds, such as quinones, tend to favor type 1 pathway 14 . The detection of singlet oxygen during...

Mitochondrial Changes

Mitochondria are perhaps the most important organelle involved in apoptosis initiation and regulation. Significant changes can be observed in mitochondrial physiology and morphology during apoptosis. In general, the apoptotic changes can be divided into two categories release of apoptotic proteins and alteration in mitochondrial functions. The released apoptotic proteins include cytochrome c, Smac Diablo, HtrA2 Omi, endonuclease G, and apoptosis-inducing factor (AIF), in addition to some nonapoptotic proteins (see Chapter 6). The redistribution of these proteins can be determined by Western blot, enzyme-linked immunosorbant assay (ELISA), or immunofluorescence staining. One major test for mitochondria functions related to apoptosis is the determination of the transmembrane potentials. Other assays have been developed to determine mitochondria permeability transition, mitochondrial generation of free radicals, mitochondria calcium content, and mitochondria pH changes (for reviews see...

Cell Adhesion Molecules

Mediators in turn promote the expression of adhesion molecules (93). Infusion of AGE products in rabbits produced a variety of vascular changes. In endothelial cells, these included increased expression of VCAM-1 and ICAM-1 mainly in areas affected by atheroma (93). Further supporting the significance of these interactions, it has been shown that blockade of receptor of advanced glycation end-products (RAGE) can inhibit AGE product-induced impairment of endothelial barrier function and consequent hyper-permeability. Inhibition of AGE product formation using antioxidants has a similar effect. More recently it has been shown that lesions from human coronary arteries from patients with diabetes when compared to lesions from nondiabetic patients, exhibit increased levels of an immunoreactive chemokine, fractalkine, that mediates firm adhesion of leukocytes (95).

Recommended readings

LaGoy, P.K. and Quirk, T.C., Establishing generic remediation goals for the polycyclic aromatic hydrocarbons critical issues, Environ. Hlth. Perspec., 102, 348-352, 1994. Lee, K.-G. and Shibamoto, T., Toxicology and antioxidant activities of non-enzymatic browning reactions products review, Food Rev. Int., 18, 151-175, 2002. Pariza, M.W., Ashoor, S.H., Chu, F.S. et al., Effects of temperature and time on mutagen

Lipoprotein Glycation Oxidation and Glyco Oxidation

It has been postulated that enhanced glycation, oxidation, and glyco-oxidation of lipoproteins may underlie the development of macrovascular disease in diabetes. This is quite an attractive hypothesis because it would explain the individual variation in the development of complications in diabetes. Regardless of the similarity in glycemic control and cardiovascular risk factors, the development of complications would also depend on differences in oxidative stress and variations in the antioxidant defenses and in differences in the immune response to the modified lipoproteins. A short summary of the large body of evidence showing that modified lipoproteins may be relevant to the accelerated development of atherosclerosis in diabetes is presented next.

Lipoprotein Oxidation and Glyco Oxidation

That oxidized or glyco-oxidized LDL indeed play an important role in the pathogen-esis of atherosclerosis has been confirmed by several lines of evidence the presence of oxidized lipoproteins in the vessel wall (161,162), as demonstrated by immunochemical staining of lesions with antibodies recognizing oxidation-specific epitopes, and the demonstration that regression of lesions may occur in animals treated with antioxidants (163). Recently, AGE epitopes have also been described in atherosclerotic lesions of euglycemic rabbits (164). Interestingly, the AGE epitopes were found in similar locations as the epitopes generated during the modification of lipoproteins by oxidation. Other studies show that blockade of RAGE results in decreased inflammation in preformed lesions in streptozotocin diabetic apo-E-deficient mice (165). Because RAGE binds to a large number of ligands, in addition to AGEs, it is not known if the effects of RAGE blockade in this study were as a result of decreased...

Characterizing Aromas In Offflavors

Exposure of beer to light has been shown to produce 3-methyl-2-butene-1-thiol, which produces a skunky off-flavor in ''sun-struck'' or ''light-struck'' ales (98,99). This mercaptan has a sensory threshold of 0.05 ppb in beer. It results from complex photo-induced degradations of isohumulones (hop-derived, bitter iso-acids) to form free-radical intermediates, which subsequently react with the thiol group of cysteine. Lightstruck off-flavor can be controlled in beer through packaging technology (colored glass bottles), use of chemically modified hop bitter acids, antioxidants, or its precipitation with high molecular weight gallotan-nins and addition of zinc salts (100). In addition to dimethyl sulfide, thioesters have been reported to contribute a cabbagy, rubbery off-note that sometimes occurs in beer, the most significant being S-methyl hexanethioate, which has a detection threshold of 1 ppb (16a). Diacetyl can produce an undesirable buttery off-character in beer through accelerated...

Possible Mechanisms Of Anticancer Effects

Because the iron necessary to catalyze hydroxyl radical production may be diet derived 88 , its chelation by PA may inhibit hydroxyl radical production and subsequent oxidative damage Figure 14.3(C) . In fact, individuals consuming less dietary fiber, and presumably less PA, have been shown to produce significantly more hydroxyl radicals 89 . Dietary PA is capable of binding iron in the digestive tract. A correlation has been observed between fecal PA and iron content 42,87 , suggesting that increased dietary PA consumption may contribute to decreased hydroxyl radical production and oxidative damage. Although Porres et al. 90 have shown that breakdown of endogenous PA in a corn-soy diet by addition of phytase enzyme can cause an increase in colonic lipid peroxidation, more research is required in this area of PA action, particularly in light of observations by Rimbach and Pallauf 86 showing no effect of PA on liver oxidant or antioxidant status even in a high iron situation.

Functional Assays of Oxidative Stress Using Genetically Engineered Escherichia coli Strains

Oxidative stress is the result of cellular imbalance between reactive oxygen species (ROS) and antioxidant defenses, in favor of the former. Oxidative stress may be induced in bacteria by many different exogenous biocidal agents and is also involved in endogenous oxygen metabolism. The oxyR operon is a main sensor of oxidative stress in bacteria and regulates the expression of several genes coding for antioxidant enzymes. Compared to wild-type cells, oxyR-deficient bacteria show enhanced sensitivity to oxidative stress and increased accumulation of intracellular ROS when exposed to prooxidants. Intracellular levels of ROS may be determined by flow cytometry using chemically reduced fluoro-genic substrates, such as dihydroethidium (hydroethidine, HE) or 2',7'-dichlorofluorescin diacetate (DCFH-DA).

Background Information

The regulation of antioxidant responses in E. coli has been studied extensively (Harvey et al., 2000 Zengh and Storz, 2000 Pomposiello and Demple, 2002). The regulon oxyR is one of the main sensors of oxidative stress in E. coli, in addition to other gene loci like soxR and soxS (Zengh et al., 2001 Droge, 2002). At least nine genes coding for proteins that are induced by low concentrations of hydrogen peroxide are under the control of oxyR and include hydro-peroxidase I (katG), alkyl hydroperoxide reductase (ahpCF), glutathione reductase (gorA), and glutaredoxin I (grxA) as well as a non-specific DNA-binding protein (dps) and a small untranslated regulatory RNA (oxyS). OxyR is a transcriptional activator existing in a reduced and an oxidized form, the latter being able to activate transcription (Storz et al., 1990). Exposure to hydrogen peroxide or induction of oxidative shift in the thiol disulfide redox status results in oxidized oxyR binding to all oxyR- regulated promoters. In...

Nonrespiratory Functions Of The Lung

Mucociliary Transport

Neutrophils can leave the pulmonary circulation and provide a secondary line of phagocytic defense in the alveoli. Phagocytes, as well as immune cells (see later discussion), may release reactive oxygen species that can cause tissue damage. However, such damage is limited by the antioxidant glutathione, which occurs in surfactant at levels 100 times higher than in other tissues. Pulmonary cells have evolved efficient mechanisms to

Products of the maillard reaction

Premelanoidins have been shown to inhibit growth, cause liver damage, and interrupt reproduction in laboratory animals. Maillard products of fructose-glycine and fructose-arginine increase the mutagenicity of 3-amino-1,4-dimethyl 5H-pyridol-(4,3-b)indole. Antimutagenic effects seem to correlate well with antioxidant effects. However, mutagenicity of benzo(a)pyrene is moderately inhibited by such products. Some products of the Maillard reaction have been shown to induce allergic reactions. Products from Maillard reactions have been found to possess antioxidant activity. Maillard reaction products are known to inhibit oxidative degradation of natural organic compounds. Not much is known about the structures of such Maillard reactions products or the mechanisms of their formation. They are found in most cooked foods and have a characteristic brown color. These antioxidant compounds have been found to be formed from histidine and glucose or arginine and xylose, with the amount produced...

Bioreactor Configurations 341 Submerged Fermentor Systems

Airlift Submerged Bioreactor

Microalgae have been used successfully, with high productivity compared to higher plants. The high productivity in these systems is due to the high biomass produced in the bioreac-tor. Microalgae have been used for preparation of vitamins, pigments, antioxidants, and fatty acids, and as feed for aquaculture. The cultivation techniques employed are open systems and closed or semiclosed outdoor photobioreactors. The common photobioreac-tors used are tubular-type and plate-type reactors (42). The cyanobacterium Spirulina platensis has been studied in batch and continuous photobioreactors under varying conditions of incident light energy and nutrient limitations (43).

Water And Wastewater Disinfection Treatment

Ionizing radiation using x-ray and gamma-ray beams with even higher energy levels than that of UV irradiation, can also be used in water, wastewater, and sludge disinfection. These ionizing mechanisms displace electrons during beam bombardment (i.e., at which point they are said to ionize), and in the presence of oxygen these displaced electrons elec-trochemically form a type of free radical (called hydroxyl radicals) that is highly toxic to microbial cells. Free radicals are highly reactive, having essentially no activation energy for their reaction. Given the acutely reactive nature of these radicals, they readily attack and destroy hydrogen bonds, double bonds, and ring structures essential to the metabolic utility of various cellular molecules. Yet another operative mechanism, and perhaps the key factor behind disinfection with ionizing irradiation, is that of a polymerizing impact (e.g., DNA thymine dimerization) whereby the biochemical effectiveness of complex molecules is...

Interactions Between Essential Fatty Acid Metabolism And Other Glucoseinduced Defects

In order to comprehend fully the consequences of perturbed essential fatty acid metabolism on nerve function, it is essential to relate these changes to other metabolic alterations that occur in diabetic neuropathy. These include elevated polyol pathway flux, effects on nitric oxide synthesis, increased oxidative stress, and formation of advanced glycation products. The importance of these abnormalities is reinforced by the fact that the treatment of experimentally diabetic rats with aldose reductase inhibitors, antioxidants and aminoguanidine, an agent that inhibits nonspecific glycation events, all tend to ameliorate physiological impairments in diabetic nerve (Sima and Sugimoto 1999). In the following sections, discussion of the interrelationship of these alterations with impaired essential fatty acid metabolism will underline the complex pathology of this disorder.

The Acute and Subacute Mouse MPTP Model

Readily absorbed and crosses the blood-brain barrier. The toxin is converted to an active toxic metabolite, 1-methyl-4-phenylpyridinium (MPP+), by the monoamine oxidase type B enzyme located in the astroglial cells (54). The produced MPP+ is taken up into the nigrostriatal DA nerve terminals selectively by the DA uptake transporter (DAT) (55). The elevated cytoplasmic MPP+ level may in turn cause the release and accumulation of the excitatory amino acid transmitter glutamate and Ca2+ within the afflicted neurons, resulting in an inhibition of complex I of the mitochondrial electron transport chain system and a production of free radicals (56,57). Impairment of respiration and oxidative damage of the mitochondria may lead to the depletion of cellular ATP and eventual neuronal death (58). Subacute MPTP injections and MPP+ production may induce apoptosis in dopaminergic neurons (59) and that could serve to initiate neuronal degeneration. On the other hand, subacute MPTP treatment causes...

Nitrates nitrites and nitrosamines

Not all cured meat products contain nitrosamines when present, they usually are in very minute amounts. Many variables influence nitrosamine levels amount of nitrite added during processing, concentrations of amines in meat, type and amounts of other ingredients used in processing, actual processing conditions, length of storage, storage temperatures, method of cooking, and degree of doneness. Inhibition of nitrosation reaction is possible. Nitrite is reduced to NO by the dehydro form of ascorbic acid. Likewise, tocopherols and other food antioxidants inhibit substitution reactions. Thus, the USDA now requires adding ascorbic acid (vitamin C) or erythorbic acid to bacon cure, a practice that greatly reduces the formation of nitrosamines.

Creatine Supplementation In Neurodegenerative Disorders

While the role of huntingtin aggregates continues to be debated, the evidence points to a proximal toxicity residing in mutant huntingtin, its proteolytic fragments, and their interactions with other proteins (Ryu and Ferrante, 2005). A secondary consequence of the gene defect may be impaired energy metabolism via mitochon-drial dysfunction (Beal, 2005). N-terminal huntingtin fragments may directly impair mitochondrial function, leading to increased oxidative damage, as mitochondria are a major source of free radicals in the cell. Indeed, it appears clear that such factors as the mass effect of cytosolic and nuclear huntingtin aggregate burden, the sequestration by huntingtin aggregates of transcription factors and neuronal proteins that are essential for neuronal survival and their subsequent reduced activity (Cha, 2000 Sugars and Rubinsztein, 2003), altered proteasomal function (Bence et al., 2001), and the localization of mutant huntingtin aggregates to cellular organelles such as...

Doxium For Varicose Veins

US 7927613 (19.04.2011) Anderson, D., Yu,T. W., Phillips, B. J. & Schmezer, P. (1994). The effect of various antioxidants and other modifying agents on oxygen-radical-generated DNA damage in human lymphocytes in the COMET assay. Mutation Research -Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 307, No. 1, (May 1994), pp. (261-270), ISSN 1386-1964 Barbieri, D., Grassilli, E., Monti, D., Salvioli, S., Franceschini, M. G., Franchini, A., Bellesia, E., Salomoni, P., Negro, P., Capri, M., Troiano, L., Cossarizza, A. & Franceschi, C. (1994). D-ribose and 2-deoxy-D-ribose induce apoptosis in human quiescent peripheral blood mononuclear cells. Biochemical and Biophysical Research Communications, Vol. 201, No. 3, (June 1994), pp. (1109-1116), ISSN 1090-2104 Barras, J. & Graf, C. (1980) Hyperviscosity in diabetic retinopathy treated with Doxium (calcium dobesilate). Vasa, Vol. 9, No. 2, (April-June 1980), pp. (161-164), ISSN0301-1526 J. (1974)....

Protection From Vitamin E And Selenium Deficiency By Phytate

We conducted an experiment to test whether the concentration and the form of inositol phosphates were important factors in determining whether phy-tate would exhibit antioxidant or pro-oxidant effects in vivo. Our lab has used a model of chronic oxidative stress induced by deficiency in vitamin E and selenium to study the adaptive responses invoked to protect rats from damage. Deficiency of these two nutrients leads to a gradual increase in oxidative stress, indicated by greater tissue concentrations of lipid oxidation products, as well as adaptations that lead to upregulation of many components of the cell's multifaceted defense system 18-21 . To determine whether phytate and Ins(1,2,3,6)P4 would exhibit antioxidant properties in vivo, these inositol phosphates were fed to rats to test whether their presence would prevent the effects of vitamin E and selenium deficiency. Inositol phosphates were prepared en-zymatically as described by Phillippy and Graf 7 . Long Evans hooded rats...

Section 2 Plant And Animal Food Applications And Functional Foods

Chapter 2.09 Potential Health Benefits of Soybean Isoflavonoids and Related Phenolic Antioxidants Chapter 2.12 Bioprocessing Strategies to Enhance l-DOPA and Phenolic Antioxidants in the Fava Bean (Vicia faba) Kalidas Shetty, Reena Randhir, and Preethi Shetty Chapter 2.26 Biochemical Markers for Antioxidant Functionality

Oxidative and Nitrosative Stress in Diabetes Induced Vascular Dysfunction

Various neurohumoral mediators and mechanical forces acting on the innermost layer of blood vessels, the endothelium, are involved in the regulation of the vascular tone. The main pathway of vasoregulation involves the activation of the constitutive, endothelial isoform of NO synthase (eNOS) resulting in NO production (53). Endothelium-depen-dent vasodilatation is frequently used as a reproducible and accessible parameter to probe endothelial function in various pathophysiological conditions. It is well established that endothelial dysfunction, in many diseases, precedes, predicts, and predisposes for the subsequent, more severe vascular alterations. Endothelial dysfunction has been documented in various forms of diabetes, and even in prediabetic individuals (52,54-58). The pathogenesis of this endothelial dysfunction involves many components including increased polyol pathway flux, altered cellular redox state, increased formation of diacylglycerol, and the subsequent activation of...

Traditional Medicine and Food Habits for Prevention of Cholera

Traditional herbal medicines (Kampo formulations) are being used in China and Japan for many centuries. The gallate compound from Rhei rhizoma inhibited cholera toxin effect in the tissue culture and fluid accumulation in the rabbit ileal loop assay 155 . The synthetic gallate has shown toxin in vivo and in vitro inhibitory effects and thus the Kampo formulation seems to be an effective adjunc-tive therapy with oral rehydration solution 155 . Soy sauce (Shoyu) was found to have antimicrobial activity against V. cholerae and other enteric bacteria along with other beneficial properties such as antihypertensive, anticarcinogenic, anticataract, antioxidant, and antiallergen 156 . Many useful herbal formulations for the treatment of cholera and other diarrheal diseases have been lost during passage of time and generations of people. Unfortunately, there was no recording system in primeval days and such formulations were kept secret for the benefit of professionals those practiced herbal...

Role For Vascular Vs Nonvascular Mechanisms

The vascular concept of PDN is seemingly supported by the recent findings with the high molecular weight metal chelator, hydroxy ethyl starch-deferoxamine (HESD), known to be confined to vascular space when administered intravenously and therefore, not to penetrate into neural elements of the peripheral nerve. Alleviation of both NBF and nerve conduction deficits (22,23), combined with reduced superoxide and peroxyni-trite formation in vasa nervorum (23), in HESD-treated streptozotocin (STZ)-diabetic rats in comparison with the corresponding untreated group could be interpreted as a proof for the key role of vascular mechanism in MNCV and SNCV deficit in early diabetes. However, it is not excluded that in vascular space, HESD is metabolized with formation of deferoxamine, with its subsequent delivery to a neural compartment of the peripheral nerve. In addition, such reactive oxygen species (ROS) as hydrogen peroxide, lipid peroxide (free form), and peroxynitrite can move from vascular...