Effect of  -tocopherol on in vitro and in vivo metabolism of low-density lipoproteins in haemodialysis patients

Yukawa, Susumu; Hibino, Akira; Maeda, Toshio; Mimura, Keiji; Yukawa, A.; Maeda, Akinori; Kishino, Masanori; Sonobe, Miyahiko; Mune, Masatoshi; Yamada, Yoichi; Niside, I.

doi:10.1093/ndt/10.supp3.1

Cited by 42 publications

(14 citation statements)

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“…The lowest levels were observed in children on maintenance HD. These results are consistent with the data obtained in adult patients with CRF [28, 29]. Moreover, Taccone-Gallucci et al [30] demonstrated the beneficial effect of vitamin E supplementation by decreasing MDA in erythrocytes of uremic patients.…”

Section: Discussionsupporting

confidence: 91%

Vitamins A, E and C as Non-Enzymatic Antioxidants and Their Relation to Lipid Peroxidation in Children with Chronic Renal Failure

Zwołińska

Grzeszczak²,

Szczepańska³

et al. 2005

Nephron Clin Pract

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Background: Increased lipid peroxidation (LP) and reduced enzymatic antioxidant defense have been observed in predialysis patients with advanced chronic renal failure (CRF) and in patients on maintenance hemodialysis (HD). To extend these observations, we evaluated the plasma, erythrocyte and dialysate levels of vitamins A and E and the plasma and dialysate levels of vitamin C as exogenous non-enzymatic antioxidants in children with CRF treated conservatively and on HD. The data obtained were related to LP monitored by erythrocyte malonyldialdehyde (E-MDA) and plasma organic hydroperoxide (OHP) concentrations. Patients: Forty-six predialysis children were enrolled in the study and divided into 2 groups: group I = moderate CRF (plasma creatinine <265.3 µmol/l), and group II = plasma creatinine ≧265.3 µmol/l. Group III consisted of 21 HD children. 27 age-matched healthy subjects served as a control group. Results: The plasma levels of vitamin A and vitamin C were significantly reduced in all CRF patients when compared to the controls, with the lowest values observed in children on maintenance HD (group III). Significant differences were also noted between the moderate CRF (group I) and HD (group III). Plasma levels of vitamin E were significantly decreased in moderate CRF (group I) and HD (group III) as compared to controls. In contrast, the erythrocyte vitamin A and vitamin E levels of predialysis children and HD patients were not different from the controls. The E-MDA and OHP concentrations in the 3 groups of CRF children were significantly higher than in healthy subjects. The concentration of plasma vitamin C was significantly inversely correlated with E-MDA, plasma OHP and creatinine in group I. In group II we found a significant correlation of plasma vitamin E levels with creatinine and E-MDA and a correlation of the plasma vitamin C concentration with E-MDA. Conclusion: CRF in children is associated with decreased concentrations of plasma antioxidant vitamins. This reduction is most expressed in children on maintenance HD and particularly concerns plasma vitamin C and erythrocyte vitamin E concentrations. The low levels of plasma vitamin A, E and C might result in reduced activity of the non-enzymatic antioxidant defense system and might be responsible for increased oxidative stress occurring in children with CRF.

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Section: Discussionsupporting

confidence: 91%

Vitamins A, E and C as Non-Enzymatic Antioxidants and Their Relation to Lipid Peroxidation in Children with Chronic Renal Failure

Zwołińska

Grzeszczak²,

Szczepańska³

et al. 2005

Nephron Clin Pract

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“…Supplementation of tocopherols leads to an increase of serum CEHC in both hemodialysis patients and healthy subjects and decreased CRP concentrations in hemodialysis patients (22,23). Thus, the accumulation of CEHC in hemodialysis patients may reflect anti-inflammatory functions contributing to the protective effects, which were shown in previous investigations dealing with vitamin E in hemodialysis patients (7,(24)(25)(26). Furthermore, one study by Saran et al (27) showed that antioxidant therapy with vitamin E resulted in lower ADMA levels in CKD patients, implying increased nitric oxide (NO) availability by vitamin E in renal patients.…”

Section: Discussionmentioning

confidence: 75%

Low Plasma α-Tocopherol Concentrations and Adverse Clinical Outcomes in Diabetic Hemodialysis Patients

Espe

Raila

Henze

et al. 2013

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Trials with the antioxidant vitamin E have failed to show benefit in the general population. Considering the different causes of death in ESRD, this study investigated the association between plasma concentrations of a-tocopherol and specific clinical outcomes in diabetic hemodialysis patients.Design, settings, participants, & measurements In 1046 diabetic hemodialysis patients (participants of the German Diabetes and Dialysis Study), a-tocopherol was measured in plasma by reversed-phase HPLC. By Cox regression analyses, hazard ratios were determined for prespecified end points according to baseline plasma a-tocopherol levels: sudden death (n=134), myocardial infarction (n=172), stroke (n=89), combined cardiovascular events (n=398), fatal infection (n=107), and all-cause mortality (n=508).Results Patients had a mean age of 6668 years, and mean plasma a-tocopherol level was 22.869.6 mmol/L. Levels of a-tocopherol were highly correlated to triglycerides (r=0.63, P,0.001). Patients in the lowest a-tocopherol quartile had (in unadjusted analyses) a 79% higher risk of stroke and a 31% higher risk of all-cause mortality compared with patients in the highest quartile. The associations were attenuated after adjustment for confounders (hazard ratio stroke =1.56, 95% confidence interval=0.75-3.25; hazard ratio mortality =1.22, 95% confidence interval=0.89-1.69, respectively). There was no association between a-tocopherol and myocardial infarction, sudden death, or infectious death.Conclusions Plasma a-tocopherol concentrations were not independently associated with cardiovascular outcomes, infectious deaths, or all-cause mortality in diabetic hemodialysis patients. The lack of association can partly be explained by a confounding influence of malnutrition, which should be considered in the planning of trials to reduce cardiovascular risk in dialysis patients.

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“…Oxidative stress induced during HD is believed to modify LDL and produce cardiovascular complications in HD patients (26,27). However, enhanced lipid peroxidation in HD patients remains a controversial issue since many recent reports have failed to confirm the increase in plasma MDA or LOOH in these patients (28,29).…”

Section: Modification Of Ldl Into Ldlmentioning

confidence: 99%

Oxidative Cross-linking of ApoB100 and Hemoglobin Results in Low Density Lipoprotein Modification in Blood

Ziouzenkova¹,

Asatryan²,

Akmal

et al. 1999

Journal of Biological Chemistry

120

106

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Human blood contains a form of minimally modified low density lipoprotein (LDL), termed LDL؊ , whose origin remains unknown. Exploring the mechanism of formation, we found that LDL ؊ can be produced in plasma in the absence of oxygen following LDL incubation with oxidized hemoglobin species. A high degree of apolipoprotein B100 modification results from covalent association of hemoglobin with LDL involving dityrosine formation but not due to the malonaldehyde epitope formation. This was evidenced by the cross-reactivity of oxidized LDL with antibodies against hemoglobin that was accompanied by a 60-fold increase in dityrosine levels. In this study we found significantly higher LDL ؊ levels in the blood of hemodialysis patients, perhaps contributing to their greatly increased risk of atherosclerosis. The mechanism of LDL ؊ formation was studied during ex vivo blood circulation using a model system resembling clinical hemodialysis in terms of the induction of inflammatory responses. This circulation increased free hemoglobin and LDL ؊ levels compared with non-circulated blood without appreciable lipid peroxidation. Pronounced increases in LDL ؊ were found also during circulation of plasma supplemented with nanomolar hemoglobin levels. The increase in dityrosine content and presence of heme in LDL after blood circulation suggest that LDL is modified, in part, by hemoglobin-LDL conjugates containing heme. Thus, hemoglobin-mediated reactions leading to LDL oxidation in plasma can account for high LDL ؊ levels in hemodialysis patients.

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Effect of -tocopherol on in vitro and in vivo metabolism of low-density lipoproteins in haemodialysis patients

Cited by 42 publications

References 0 publications

Vitamins A, E and C as Non-Enzymatic Antioxidants and Their Relation to Lipid Peroxidation in Children with Chronic Renal Failure

Vitamins A, E and C as Non-Enzymatic Antioxidants and Their Relation to Lipid Peroxidation in Children with Chronic Renal Failure

Low Plasma α-Tocopherol Concentrations and Adverse Clinical Outcomes in Diabetic Hemodialysis Patients

Oxidative Cross-linking of ApoB100 and Hemoglobin Results in Low Density Lipoprotein Modification in Blood

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