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      Reactive Oxygen Metabolites: A Link between Oxidative Stress and Inflammation in Patients on Hemodialysis

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          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.

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          Most cited references 19

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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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              Oxidative stress and inflammation in hemodialysis patients.

              Dialysis is associated with an increased generation of oxidants, which play an important part in the development of endothelial dysfunction and atherogenesis. Markers of oxidative stress include F2-isoprostanes and ethane. Measurements in dialysis patients before dialysis showed higher levels of esterified plasma F2-isoprostanes (1.62 +/- 0.73 ng/mL) than in control subjects (0.27 +/- 0.10 ng/mL) (P 16.8 mg/L) levels were more than twice as likely to die as patients with low CRP levels (relative risk [RR] = 2.16; 95% confidence interval [CI], 1.50-3.09). CRP values were a significant predictor of mortality even after controlling for diabetes, albumin, ferritin, and age at commencement of dialysis. The RR for CRP after adjustment was 1.58 (95% CI, 1.06-2.34, P = 0.024). There were no significant interactions between CRP and other predictors of mortality, indicating that high CRP levels have an additive effect on the mortality risk. These findings show that hemodialysis patients are exposed to both oxidative stress and inflammation.

                Author and article information

                Blood Purif
                Blood Purification
                S. Karger AG
                March 2007
                11 January 2007
                : 25
                : 2
                : 175-178
                aBiochemical Department and bRenal Unit, Alexandra Hospital, Athens, Greece
                98521 Blood Purif 2007;25:175–178
                © 2007 S. Karger AG, Basel

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                Page count
                Figures: 1, Tables: 2, References: 26, Pages: 4
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/98521
                Original Paper


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