1. ¹Section of Nephrology, Department of Biopathology and Imaging Techniques, Tor Vergata University, Rome, Italy
2. ²Department of Biomedical Sciences, University of Teramo, Teramo, Italy
3. ³Neuroimmunology Unit, S Lucia Foundation IRCCS, Rome, Italy

Correspondence: M Taccone-Gallucci, Section of Nephrology, Department of Biopathology and Imaging Terchniques, Tor Vergata University, Via Casilina 1049, Rome 00169, Italy. E-mail: taccone.gallucci@med.uniroma2.it; M Maccarrone, Department of Biomedical Sciences, University of Teramo, Piazza A Moro 45, Teramo 64100, Italy. E-mail: mmaccarrone@unite.it

Received 6 January 2005; Revised 1 July 2005; Accepted 8 July 2005; Published online 8 March 2006.

Abstract

Reactive oxygen species formation and release of pro-inflammatory/pro-atherogenic cytokines, that is, interleukin 1- and tumor necrosis factor-, need the activation of the arachidonic acid cascade via the enzyme 5-lipoxygenase (5-Lox). 5-Lox activity and expression are significantly increased in peripheral blood mononuclear cells (PBMCs) of end-stage renal disease (ESRD) patients on maintenance hemodialysis (HD). Diets enriched with n-3 polyunsaturated fatty acids (PUFAs) (-3) have been associated to a lower incidence of coronary heart disease (CHD) and a reduction in atherosclerotic lesions. -3 may interfere with the arachidonic acid cascade by inhibiting 5-Lox. Lipid peroxidation, leukotriene B₄ (LTB₄) production, 5-Lox activity and expression were investigated in PBMC isolated from ESRD patients under maintenance HD before and after a 3-month oral supplementation with -3 at a daily dose of 2700 mg of n-3 PUFAs at the average eicosapentaenoic acid/docosaesaenoic acid ratio of 1.2 and finally after a further 3-month washout with no -3 supplementation. PBMCs from non-uremic volunteers were also investigated for comparison to normal parameters. Administration of -3 reduced significantly lipid peroxidation (P<0.0001), LTB₄ synthesis (P<0.0001) and 5-Lox activity (P<0.0001), with no effect on 5-Lox protein expression. After the 3-month washout, all parameters were comparable to those observed before treatment. Our results resemble those obtained after oral administration of vitamin E and are consistent with a reversible, dose-dependent inhibition of 5-Lox by -3. Upregulation of 5-Lox may also be related to the increased mitochondrial damage and apoptosis of PBMCs observed in ESRD patients compared to non-uremic controls. -3 may thus protect PBMCs of ESRD patients against oxidative stress.