Vitamin E-coated dialyzers reduce oxidative stress related proteins and markers in hemodialysis--a molecular biological approach.
BACKGROUND
Hemodialysis patients (HD) are exposed to oxidative stress which contributes to cardiovascular disease and accelerated atherosclerosis, major causes of mortality in these patients. A new dialysis membrane coated with vitamin E has been proposed against oxidative stress and atherosclerosis due to their ability to inhibit lipid peroxidation by interacting with scavengers. The mechanisms however are not completely clarified. This study evaluated, using a molecular biology approach, the effect of 6 months treatment with vitamin E-modified dialyzers, CL-E, on the gene expression of oxidative stress related proteins and markers.


METHODS
To this end, the gene expression of p22phox, a NAD(P)H oxidase subunit closely linked with the generation of superoxide anions and of Heme oxygenase-1 (HO-1), induced by and protective from oxidative stress, were evaluated by RT-PCR in mononuclear cells from 5 patients under 3 times a week chronic bicarbonate dialysis. Hydroperoxide (HPO) and total antioxidant power (AOP) plasma levels were evaluated at 3 and 6 months of treatment. HPO was also evaluated in 8 patients under CL-E treatment for 1 year and compared with 8 patients treated with cuprammonium-ryon filter (TAF).


RESULTS
p22phox mRNA decreased from 0.61 +/- 0.05 d.u. to 0.48 +/- 0.03, p < 0.01 while HO-1 increased from 0.55 +/- 0.04 d.u. to 0.62 +/- 0.03, p < 0.01. HPO decreased in CL-E treated patients: from 2.72 +/- 0.26 microM to 1.45 +/- 0.27 at 3 months (p < 0.001) to 0.87 +/- 0.11, p < 0.001 at 6 months, while AOP increased: from 752 +/- 90 mmol/L to 1057 +/- 105, p < 0.001 at 6 months. HPO was also reduced in 1 year Excebrane CL-E treated patients compared with cuprammonium treated patients: 2.25 +/- 0.3 vs. 1.42 +/- 0.11 microM, p < 0.001.


CONCLUSIONS
The reduced expression of oxidative stress related proteins and markers gives further support to the efficacy of the use of Vitamin E coated dialysers for the prevention or slowing progression of cardiovascular disease and atherosclerosis, major complications and causes of mortality in these patients in which oxidative stress plays a pivotal role.
Calò
L A
LA
Department of Clinical and Experimental Medicine, Clinica Medica 4, University of Padova-Azienda Ospedaliera di Padova, Italy. renzcalo@unipd.it
Naso
A
A
Pagnin
E
E
Davis
P A
PA
Castoro
M
M
Corradin
R
R
Riegler
P
P
Cascone
C
C
Huber
W
W
Piccoli
A
A
D000368:Aged; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D020099:Coated Materials, Biocompatible; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000187:drug effects / Q000235:genetics; D051547:Heme Oxygenase-1; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000235:genetics; D008567:Membranes, Artificial; D008875:Middle Aged; D009252:NADPH Dehydrogenase / Q000187:drug effects / Q000235:genetics; D019255:NADPH Oxidases; D018384:Oxidative Stress / Q000187:drug effects*; D010750:Phosphoproteins / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000097:blood; D006435:Renal Dialysis / Q000295:instrumentation*; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D015415:Biomarkers; D020099:Coated Materials, Biocompatible; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D008567:Membranes, Artificial; D010750:Phosphoproteins; D012333:RNA, Messenger; D014810:Vitamin E; D006861:Hydrogen Peroxide; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D019255:NADPH Oxidases; C086986:CYBA protein, human; D009252:NADPH Dehydrogenase