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      About Blood Purification: 3.0 Impact Factor I 5.6 CiteScore I 0.83 Scimago Journal & Country Rank (SJR)

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      Reactive oxygen metabolites: a link between oxidative stress and inflammation in patients on hemodialysis.

      Blood purification
      Adult, Aldehydes, blood, Antioxidants, metabolism, C-Reactive Protein, Female, Humans, Inflammation, etiology, Lipid Peroxides, Male, Malondialdehyde, Middle Aged, Oxidative Stress, physiology, Reactive Oxygen Species, Renal Dialysis, adverse effects

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          Abstract

          Oxidative stress plays a significant role in the development of inflammation in patients undergoing hemodialysis (HD). This study intends to evaluate the relationship between C-reactive protein (CRP) and the newly established marker of lipid peroxidation, d-ROMs (reactive oxygen metabolites), in comparison with different indicators of oxidative stress. Plasma total antioxidant capacity (TAC), lipid peroxidation products malonaldehyde (MDA) and 4-hydroxyalkenals, as well as d-ROMs, were determined in 24 patients before HD and in 21 normal controls (NC). It was found that HD patients had higher levels of d-ROMs than NC (p = 0.033). A highly significant positive correlation was observed between logCRP and d-ROMs concentrations (p < 0.0001, r = 0.85) in patients, but not in NC. The concentrations of TAC and MDA were not associated with CRP in HD or in NC individuals. It is concluded that d-ROMs concentration is a potent marker of oxidative injury that is strongly indicative of the inflammatory status in HD patients. Copyright 2007 S. Karger AG, Basel.

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          The measurement and mechanism of lipid peroxidation in biological systems.

          The basic chemistry of the propagation of lipid peroxidation reactions has been known for years, but the mechanism of initiation of this process in biological membrane systems is still uncertain. Currently available assays for measuring peroxidation are reviewed--the more specific the assay used, the less peroxide is found in healthy human tissues and body fluids. Lipid peroxidation can arise as a consequence of tissue injury in many disease states and may sometimes contribute significantly to worsening the tissue injury.
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            Oxidant mechanisms in toxic acute renal failure.

            Over the last decade, there has been accumulating evidence for a role of reactive oxygen metabolites in the pathogenesis of a variety of renal diseases, including gentamicin, glycerol, and cyclosporine A models of toxic acute renal failure. Gentamicin has been shown in both in vitro and in vivo studies to enhance the generation of reactive oxygen metabolites. Iron is important in models of tissue injury, presumably because it is capable of catalyzing free radical formation. Gentamicin has been shown to cause release of iron from renal cortical mitochondria. Scavengers of reactive oxygen metabolites as well as iron chelators provide protection in gentamicin-induced nephrotoxicity. In glycerol-induced acute renal failure, an animal model of rhabdomyolysis, there is enhanced generation of hydrogen peroxide, and scavengers of reactive oxygen metabolites and iron chelators provide protection. Although the dogma is that the myoglobin is the source of iron, the results of recent studies suggest that cytochrome P-450 may be an important source of iron in this model. In addition, there are marked alterations in antioxidant defenses, such as glutathione, as well as changes in heme oxygenase. Cyclosporine A has been shown to enhance the generation of hydrogen peroxide in vitro and lipid peroxidation in vitro and in vivo. Antioxidants have been shown to be protective in cyclosporine A nephrotoxicity. This collective body of evidence suggests an important role for reactive oxygen metabolites in toxic acute renal failure and may provide therapeutic opportunities of preventing or treating acute renal failure in humans.
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              Plasma total antioxidant capacity in hemodialyzed patients and its relationships to other biomarkers of oxidative stress and lipid peroxidation.

              Patients undergoing long-term hemodialysis (HD) exhibit increased levels of oxidative stress, likely contributing to the increased rate of cardiovascular disease. The present study represents a critical evaluation of some of the most widely used oxidative indicators, as applied to the monitoring of hemodialysis-associated oxidative stress. Total plasma antioxidant capacity was determined by two independent procedures, the total antioxidant status (TAS) and the ferric reducing ability of plasma (FRAP) methods. Plasma lipid peroxidation was assessed by determining the peroxidation products malonaldehyde and 4-hydroxynonenal (MDA-4HNE) as well as lipid hydroperoxides ("Fox-2" and "d-ROMs" methods). Total plasma thiols and plasma alpha-tocopherol were also determined. MDA-4HNE levels were higher in HD patients and decreased following HD, possibly due to passive diffusion across dialysis filters. d-ROMs were also higher in HD patients but exhibited a further increase following the dialysis procedure. Serum alpha-tocopherol did not show any significant differences. Plasma thiols were lower in HD patients and were restored following HD. Plasma total antioxidant capacity determined with either method was unexpectedly higher in HD patients compared to controls, and decreased following HD. These data indicate that, of the biomarkers studied, d-ROMs level is the one more accurately reflecting the oxidative alterations taking place in HD patients, while determination of MDA-4HNE fails to detect oxidation occurring during the HD sessions. In addition, our findings point out that the determination of total antioxidant capacity in HD patients is severely affected by the concomitant fluctuations in plasma urate levels and therefore needs careful interpretation.
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