Oxidative stress antioxidants

Reactive Oxygen Species Antioxidants Oxidative Stress... 

Superoxide radical anion, hydroxyl radical, and hydrogen peroxide are known as prooxidants, whereas substances that neutralize their effects are called antioxidants. Oxidative stress occurs when the prooxidant-antioxidant balance becomes too favorable to the prooxidants. The effects of prooxidants can be neutralized by their direct reaction with small-molecule antioxidants, including glutathione, ascorbate, and tocopherols. In addition, oxidizing radicals are scavenged from a living system by several enzymes, including peroxidase, superoxide dismutase, and catalase. Oxidative lesions on DNA may be repaired by DNA repair enzymes. 

The defense enzyme superoxide dismutase (SOD) removes the superoxide free radical. Catalase and glutathione peroxidase remove hydrogen peroxide and lipid peroxides. Vitamin E, vitamin C, and plant flavonoids act as antioxidants. Oxidative stress occurs when the rate of ROS generation exceeds the capacity of the cell for their removal (Fig. 24.2). 

Cadenas E, Packer L (2002) Handbook of antioxidants (oxidative stress and desease). Marcel Dekker, New York... 

Although the harmful effects of free radicals in biological systems were discovered about half a century ago, the importance of free radicals and antioxidants, and the therapeutic potential of the latter in health and disease, has only become clear in recent years [7], Usually, low or moderate concentrations of ROS and RNS form part of the development process of cellular structures and the host cellular defense mechanisms such as the phagocytic destruction of bacteria [2,7]. Normally, there is a balance between the formation and removal of these free radicals. However, when this balance is shifted towards overproduction of free radicals or the removal of free radicals is diminished as a result of a shortage of antioxidants, oxidative stress develops. Because these free radicals have an affinity for nucleic acids, proteins and lipids, they play a pivotal role under conditions of oxidative stress in the development of a number of chronic and degenerative diseases (see Figure 11.2) [9,7], Recently, it has been claimed that oxidative stress in saliva may play an important role in the onset of periodontal diseases [11], Furthermore the oxidative stress in patients with periodontal disease could lead to the development of cardiovascular disease [12]. 

It has been proposed that the development of the complications of diabetes mellitus may be linked to oxidative stress and therefore might be attenuated by antioxidants such as vitamin E. Furthermore, it is discussed that glucose-induced vascular dysfunction in diabetes can be reduced by vitamin E treatment due to the inactivation of PKC. Cardiovascular complications are among the leading causes of death in diabetics. In addition, a postulated protective effect of vitamin E (antioxidants) on fasting plasma glucose in type 2 diabetic patients is also mentioned but could not be confirmed in a recently published triple-blind, placebo-controlled clinical trial [3]. To our knowledge, up to now no clinical intervention trials have tested directly whether vitamin E can ameliorate the complication of diabetes. 

As the above mentioned studies with high supplementation dosages exemplarily show, there is no known toxicity for phylloquinone (vitamin Kl), although allergic reactions are possible. This is NOT true for menadione (vitamin K3) that can interfere with glutathione, a natural antioxidant, resulting in oxidative stress and cell membrane damage. Injections of menadione in infants led to jaundice and hemolytic anemia and therefore should not be used for the treatment of vitamin K deficiency. 

More recently, large human intervention trials were undertaken with P-carotene alone, or in combination with non-dietary amounts of vitamin E. These trials were undertaken because of promising animal studies that suggested that these antioxidants could offer chemo-preventive action against oxidative stress. The results, which are summarised in Table 11.1, were disappointing. Although the study population in two of the studies (ATBC and CARET)... 

Mincing, cooking and maturing expose meat products to oxidative stress for a long time so that antioxidants added for lipid protection are slowly destroyed on storage. Onion juice is a powerful antioxidant in meat products, more efficient than garlic juice. Lipid hydroperoxides are reduced to inactive hydroxyl derivatives by reaction with sulphur compounds present in those juices. 

L (1999) Effect of parsley intake on urinary apigenin excretion, blood antioxidant enzymes and on biomarkers for oxidative stress in hiunans, Brit J Nutr, 81, 447-55. 

The protective effects of carotenoids against chronic diseases appear to be correlated to their antioxidant capacities. Indeed, oxidative stress and reactive oxygen species (ROS) formation are at the basis of oxidative processes occurring in cardiovascular incidents, cancers, and ocular diseases. Carotenoids are then able to scavenge free radicals such as singlet molecular oxygen ( O2) and peroxyl radicals particularly, and protect cellular systems from oxidation. 

Curcumin possesses strong antioxidant capacities, which may explain its effects against degenerative diseases in which oxidative stress plays a major role. As previously described for flavonoids, it is unlikely that curcumin acts as a direct antioxidant outside the digestive tract since its concentration in peripheral blood and organs is very low (near or below 1 pM, even after acute or long-term supplementation). Indeed, it has been shown that the intestinal epithelium limits its entry into the body, as reflected by absorption studies in various models (portal blood perfusion, everted bags). ... 

Betalains have shown strong antioxidant activities in biological environments such as membranes and LDLs," -" suggesting that the consumption of betalain-colored foods may exert protective effects against certain oxidative stress-related diseases (i.e., cancers) in humans. Beetroot has been used as a treatment for cancer in Europe for several centuries. The high content of betanin in red beetroot (300 to 600 mg/kg) may be the explanation for the purported cancer chemopreventive effects of beets. 

As mentioned earlier, physiological concentrations of carotenoids in vivo are in the micromolar range, mainly because of limited bioavailabiUty. Also, the antioxidant efficiencies of carotenoids after absorption are probably limited. Concentrations before absorption are much higher and can justify possible antioxidant actions in vivo. To test this hypothesis, Vulcain et al. developed an in vitro system of lipid peroxidation in which the oxidative stress is of dietary origin (metmyoglobin from meat) and different types of antioxidants (carotenoids, phenols) are tested. 

Experimental evidence in humans is based upon intervention studies with diets enriched in carotenoids or carotenoid-contaiifing foods. Oxidative stress biomarkers are measured in plasma or urine. The inhibition of low density lipoprotein (LDL) oxidation has been posmlated as one mechanism by which antioxidants may prevent the development of atherosclerosis. Since carotenoids are transported mainly via LDL in blood, testing the susceptibility of carotenoid-loaded LDL to oxidation is a common method of evaluating the antioxidant activities of carotenoids in vivo. This type of smdy is more precisely of the ex vivo type because LDLs are extracted from plasma in order to be tested in vitro for oxidative sensitivity after the subjects are given a special diet. 

Results obtained in in vivo and ex vivo experiments are of various types. Some studies have found positive effects of the consumption of carotenoids or foods containing carotenoids on the markers of in vivo oxidative stress, even in smokers. Other studies demonstrated no effects of carotenoid ingestion on oxidative stress biomarkers of lipid peroxidation. " It should be noted that for studies using food, the activity observed may also be partly due to other antioxidant molecules in the food (phenols, antioxidant vitamins) or to the combination of actions of all the antioxidants in the food. 

Stocker, R. and Frei, B. (1991). Endogenous antioxidant defences in human plasma. In Oxidative Stress, Oxidants and Antioxidants (ed. H. Sies) pp. 213-243, Academic Press, London. 

Whilst experimentally it is relatively easy to investigate the eflFect of the exogenous application of GSH and GSSG on cardiac Na/K ATPase activity, one further approach that has been exploited in many aspects of oxidant-induced cell injury has been the depletion of cellular glutathione levels. The hypothesized importance of GSH in the cell s antioxidant armoury would be expected to be reflected in an increased susceptibility to oxidant stress-... 

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