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      Antioxidant Supplementation in Renal Replacement Therapy Patients: Is There Evidence?

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          Abstract

          The disruption of balance between production of reactive oxygen species and antioxidant systems in favor of the oxidants is termed oxidative stress (OS). To counteract the damaging effects of prooxidant free radicals, all aerobic organisms have antioxidant defense mechanisms that are aimed at neutralizing the circulating oxidants and repair the resulting injuries. Antioxidants are either endogenous (the natural defense mechanisms produced by the human body) or exogenous, found in supplements and foods. OS is present at the early stages of chronic kidney disease, augments progressively with renal function deterioration, and is further exacerbated by renal replacement therapy. End-stage renal disease patients, on hemodialysis (HD) or peritoneal dialysis (PD), suffer from accelerated OS, which has been associated with increased risk for mortality and cardiovascular disease. During HD sessions, the bioincompatibility of dialyzers and dialysate trigger activation of white blood cells and formation of free radicals, while a significant loss of antioxidants is also present. In PD, the bioincompatibility of solutions, including high osmolality, elevated lactate levels, low pH, and accumulation of advanced glycation end-products trigger formation of prooxidants, while there is significant loss of vitamins in the ultrafiltrate. A number of exogenous antioxidants have been suggested to ameliorate OS in dialysis patients. Vitamins B, C, D, and E, coenzyme Q10, L-carnitine, a-lipoic acid, curcumin, green tea, flavonoids, polyphenols, omega-3 polyunsaturated fatty acids, statins, trace elements, and N-acetylcysteine have been studied as exogenous antioxidant supplements in both PD and HD patients.

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          Vitamin E consumption and the risk of coronary heart disease in men.

          The oxidative modification of low-density lipoproteins increases their incorporation into the arterial intima, an essential step in atherogenesis. Although dietary antioxidants, such as vitamin C, carotene, and vitamin E, have been hypothesized to prevent coronary heart disease, prospective epidemiologic data are sparse. In 1986, 39,910 U.S. male health professionals 40 to 75 years of age who were free of diagnosed coronary heart disease, diabetes, and hypercholesterolemia completed detailed dietary questionnaires that assessed their usual intake of vitamin C, carotene, and vitamin E in addition to other nutrients. During four years of follow-up, we documented 667 cases of coronary disease. After controlling for age and several coronary risk factors, we observed a lower risk of coronary disease among men with higher intakes of vitamin E (P for trend = 0.003). For men consuming more than 60 IU per day of vitamin E, the multivariate relative risk was 0.64 (95 percent confidence interval, 0.49 to 0.83) as compared with those consuming less than 7.5 IU per day. As compared with men who did not take vitamin E supplements, men who took at least 100 IU per day for at least two years had a multivariate relative risk of coronary disease of 0.63 (95 percent confidence interval, 0.47 to 0.84). Carotene intake was not associated with a lower risk of coronary disease among those who had never smoked, but it was inversely associated with the risk among current smokers (relative risk, 0.30; 95 percent confidence interval, 0.11 to 0.82) and former smokers (relative risk, 0.60; 95 percent confidence interval, 0.38 to 0.94). In contrast, a high intake of vitamin C was not associated with a lower risk of coronary disease. These data do not prove a causal relation, but they provide evidence of an association between a high intake of vitamin E and a lower risk of coronary heart disease in men. Public policy recommendations with regard to the use of vitamin E supplements should await the results of additional studies.
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            Vitamin E consumption and the risk of coronary disease in women.

            Interest in the antioxidant vitamin E as a possible protective nutrient against coronary disease has intensified with the recognition that oxidized low-density lipoprotein may be involved in atherogenesis. In 1980, 87,245 female nurses 34 to 59 years of age who were free of diagnosed cardiovascular disease and cancer completed dietary questionnaires that assessed their consumption of a wide range of nutrients, including vitamin E. During follow-up of up to eight years (679,485 person-years) that was 97 percent complete, we documented 552 cases of major coronary disease (437 nonfatal myocardial infarctions and 115 deaths due to coronary disease). As compared with women in the lowest fifth of the cohort with respect to vitamin E intake, those in the top fifth had a relative risk of major coronary disease of 0.66 (95 percent confidence interval, 0.50 to 0.87) after adjustment for age and smoking. Further adjustment for a variety of other coronary risk factors and nutrients, including other antioxidants, had little effect on the results. Most of the variability in intake and reduction in risk was attributable to vitamin E consumed as supplements. Women who took vitamin E supplements for short periods had little apparent benefit, but those who took them for more than two years had a relative risk of major coronary disease of 0.59 (95 percent confidence interval, 0.38 to 0.91) after adjustment for age, smoking status, risk factors for coronary disease, and use of other antioxidant nutrients (including multi-vitamins). Although these prospective data do not prove a cause-and-effect relation, they suggest that among middle-aged women the use of vitamin E supplements is associated with a reduced risk of coronary heart disease. Randomized trials of vitamin E in the primary and secondary prevention of coronary disease are being conducted; public policy recommendations about the widespread use of vitamin E should await the results of these trials.
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              Silymarin as a Natural Antioxidant: An Overview of the Current Evidence and Perspectives

              Silymarin (SM), an extract from the Silybum marianum (milk thistle) plant containing various flavonolignans (with silybin being the major one), has received a tremendous amount of attention over the last decade as a herbal remedy for liver treatment. In many cases, the antioxidant properties of SM are considered to be responsible for its protective actions. Possible antioxidant mechanisms of SM are evaluated in this review. (1) Direct scavenging free radicals and chelating free Fe and Cu are mainly effective in the gut. (2) Preventing free radical formation by inhibiting specific ROS-producing enzymes, or improving an integrity of mitochondria in stress conditions, are of great importance. (3) Maintaining an optimal redox balance in the cell by activating a range of antioxidant enzymes and non-enzymatic antioxidants, mainly via Nrf2 activation is probably the main driving force of antioxidant (AO)  action of SM. (4) Decreasing inflammatory responses by inhibiting NF-κB pathways is an emerging mechanism of SM protective effects in liver toxicity and various liver diseases. (5) Activating vitagenes, responsible for synthesis of protective molecules, including heat shock proteins (HSPs), thioredoxin and sirtuins and providing additional protection in stress conditions deserves more attention. (6) Affecting the microenvironment of the gut, including SM-bacteria interactions, awaits future investigations. (7) In animal nutrition and disease prevention strategy, SM alone, or in combination with other hepatho-active compounds (carnitine, betaine, vitamin B12, etc.), might have similar hepatoprotective effects as described in human nutrition.
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                Author and article information

                Contributors
                Journal
                Oxid Med Cell Longev
                Oxid Med Cell Longev
                OMCL
                Oxidative Medicine and Cellular Longevity
                Hindawi
                1942-0900
                1942-0994
                2019
                15 January 2019
                : 2019
                : 9109473
                Affiliations
                1Division of Nephrology and Hypertension, 1st Department of Internal Medicine, AHEPA Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
                2Department of Nephrology, Medical School, University of Ioannina, Ioannina, Greece
                Author notes

                Guest Editor: Mansur A. Sandhu

                Author information
                http://orcid.org/0000-0002-7564-2724
                http://orcid.org/0000-0001-9302-1633
                http://orcid.org/0000-0002-1172-1829
                Article
                10.1155/2019/9109473
                6350615
                30774749
                77e2d36b-1345-415a-81ea-8d6de8e9d354
                Copyright © 2019 Vassilios Liakopoulos et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 October 2018
                : 15 December 2018
                : 20 December 2018
                Categories
                Review Article

                Molecular medicine
                Molecular medicine

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