Massimo Taccone-Gallucci

Vitamin E suppresses 5-lipoxygenase-mediated oxidative stress in peripheral blood mononuclear cells of hemodialysis patients regardless of administration route

A number of pathological conditions caused by oxidative stress have been reported in uremic patients undergoing maintenance hemodialysis (HD). Enhanced lipid peroxidation was previously observed in peripheral blood mononuclear cells (PBMCs) of HD patients. Upregulation of 5-lipoxygenase (5-Lox) activity and protein content with enhanced production of leukotriene B(4) (LTB(4)) and membrane lipoperoxides was also shown in PBMCs of HD patients. Administration of free vitamin E specifically inhibited 5-Lox activity without affecting gene expression at the protein level. To assess whether oral or intramuscular (IM) administration of vitamin E may suppress 5-Lox in HD patients, PBMCs from 16 subjects on maintenance HD therapy for at least 6 months were investigated before and after a short course of IM or oral administration of vitamin E (8 patients per group). PBMCs from 13 healthy controls were also evaluated and assumed as the reference standard. Vitamin E significantly reduced lipid peroxidation, LTB(4) content, and 5-Lox activity in PBMCs, whereas 5-Lox gene expression at the protein level was not affected. There were no significant differences in these parameters between patients treated with IM or oral vitamin E. PBMCs of HD patients showed enhanced membrane lipid peroxidation and release of LTB(4), both linked to upregulation of 5-LOX: 5-Lox activity and related oxidative stress were significantly (although not completely) suppressed by vitamin E regardless of the administration route.

Red Blood Cell Membrane Lipid Peroxidation in Continuous Ambulatory Peritoneal Dialysis Patients

We have recently described that in the erythrocytes from uremic patients on chronic hemodialysis, the pentose-phosphate shunt is defective, the membrane concentrations of malonyldialdehyde, resulting from peroxidation of polyunsaturated fatty acids in the membranes themselves, are increased, and the concentrations of vitamin E, an antioxidizing agent, are reduced. In the present study we have analyzed these same metabolic aspects in a group of uremic patients in continuous ambulatory peritoneal dialysis. We have found normal function of the pentose-phosphate shunt, slightly elevated concentrations of malonyldialdehyde compared to controls, but definitely lower than in chronic hemodialysis patients, and higher tocopherol concentrations than in both controls and chronic hemodialysis patients.

Chronic treatment with statins increases the availability of selenium in the antioxidant defence systems of hemodialysis patients.

PROJECT Oxidative stress (OS) is enhanced in hemodialysis (HD) patients. Lipid peroxidation and oxidative damage to glycids, proteins and nucleic acids are the main consequences of OS and are associated with increased cardiovascular risk. Vitamin E and glutathione peroxidase (GSH-Px) represent the main antioxidant systems in human cells. Selenium (Se), bound to the active sites of GSH-Pxs, plays a critical role in this antioxidant defence system. Statins are widely used and extensively investigated in the prevention of cardiovascular disease, notably in high-risk subjects. Several studies show antioxidant effects of statins not related to their lipid-lowering action. Our study aimed to compare serum Se concentration in ESRD patients on maintenance HD and in homogeneous healthy subjects and to investigate whether chronic treatment with statins may interfere with serum Se concentration in HD patients. PROCEDURE A total of 103 HD patients and 69 healthy subjects were enrolled; HD patients were divided into patients who were not treated with statins (group A) and patients who assumed statins since 6 months at least (group B). Serum Se was determined by atomic absorption spectrometry. RESULTS Serum Se was significantly lower in HD patients of group A compared with healthy subjects (81.65+/-19.66 Vs. 96.47+/-15.62 mcg/L, p<0.0040). However, in HD patients who assumed statins serum, Se was significantly higher than in HD patients who did not (111.83+/-18.82 vs. 81.65+/-19.66 mcg/L, p<0.0001). CONCLUSIONS Our results suggest that in HD patients chronic treatment with statins is related to higher-serum Se concentration.

Acid-base balance and oxygen tension during dialysis in uremic patients with chronic obstructive pulmonary disease.

Recent reports on the effects of dialysis on acid-base balance and metabolic acidosis correction in end-stage renal disease (ESRD) patients with chronic obstructive pulmonary disease (COPD) are lacking. Here, we compared acid-base balance and blood gasses among 14 patients with established COPD (group A) and eight patients with normal respiratory function (group B). The two groups were homogeneous for age, time on dialysis, and male/female ratio. At the beginning of dialysis, acid-base balance and blood gasses were comparable between patients of groups A and B. A significant difference between groups was observed only in pCO(2) at 20 min, together with a delay in pH increase. Effective correction of acidosis was reported at the end of dialysis and is not significantly affected by COPD. Nevertheless, weight loss must be carefully monitored in these patients in order to prevent hyperhydration and worsening of respiratory function.

Vitamin E-Related Inhibition of Monocyte 5-Lipoxygenase and Cardiovascular Outcome in Maintenance Hemodialysis Patients

A daily supplement of vitamin E is recommended for the secondary prevention of cardiovascular events in end-stage renal disease patients on maintenance hemodialysis. Vitamin E has been entrusted with therapeutic properties against cardiovascular disease for more than 60 years. Several epidemiological studies and intervention trials have been performed with vitamin E, and some of them showed that it prevents atherosclerosis. For a long time, vitamin E was assumed to act by decreasing the oxidation of low-density lipoproteins, a key step in atherosclerosis initiation. However, at the cellular level vitamin E interferes with smooth muscle cell proliferation, platelet aggregation, monocyte adhesion, and oxidized low-density lipoproteins uptake and cytokine production, all reactions implied in the progression of atherosclerosis. Recent research points out that these effects may be not only the result of the antioxidant activity of vitamin E but also of its distinct molecular actions. These biological properties of vitamin E may allow to design better strategies for primary and secondary prevention of cardiovascular disease, with a potential exploitation of vitamin E supplements in primary and secondary prevention of major adverse cardiovascular events in all uremic patients. In this review, we also outline relevant patents on vitamin E and lipoxygenase inhibitors.

Administration of GSH has no influence on the RBC membrane: oxidative damage to patients on hemodialysis.

In patients on hemodialysis, a metabolic block of the pentose phosphate shunt has been described that impairs the reduction of oxidized glutathione. The block results in lack of detoxication of the free hydroxyl radicals produced inside the red blood cell (RBC) and causes oxidative damage to the polyunsaturated fatty acids of the RBC membrane that results in formation of aldehydes. Malonyldialdehyde has been used as an index of the oxidative damage. In a study group of 13 patients on hemodialysis, the authors have tested whether administering reduced glutathione (GSH) at 1200 mg/day for 1 month could minimize oxidative damage to the RBC membranes and improve the hematologic parameters. Treatment with GSH was followed by significant improvement of hematocrit (P = 0.008), hemoglobin (P = 0.03), and RBC count (P = 0.0037); however, oxidative damage to the membranes was increased (P = 0.0004), which suggests that improvement of the hematologic parameters is not related to reduction of the oxidative damage. This is because oxidized glutathione, formed in the oxidative process, cannot be reduced back to GSH because of alteration of the pentose phosphate shunt.

Red blood cell membrane oxidative damage and renal impairment in uremic patients under conservative treatment.

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Dialysis leukopenia and hypoxemia in a patient without measurable complement activity.

SummaryWe have studied complement activity, total leukocyte counts,

N-3 PUFAs reduce oxidative stress in ESRD patients on maintenance HD by inhibiting 5-lipoxygenase activity

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