title: Vitamin E suppresses 5-lipoxygenase-mediated oxidative stress in peripheral blood mononuclear cells of hemodialysis patients regardless of administration route.
abstract: 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.
authors.affiliation: Departments of Experimental Medicine and Biochemical Sciences, Nephrology, and Surgery, Tor Vergata University, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Maccarrone
authors.forename: C
authors.initials: C
authors.lastname: Meloni
authors.forename: S
authors.initials: S
authors.lastname: Manca-di-Villahermosa
authors.forename: N
authors.initials: N
authors.lastname: Cococcetta
authors.forename: C U
authors.initials: CU
authors.lastname: Casciani
authors.forename: A
authors.initials: A
authors.lastname: Finazzi-Agrò
authors.forename: M
authors.initials: M
authors.lastname: Taccone-Gallucci
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000704:Analysis of Variance; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007273:Injections, Intramuscular; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism*; D008563:Membrane Lipids / Q000032:analysis / Q000378:metabolism*; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D006435:Renal Dialysis; D015854:Up-Regulation; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D008563:Membrane Lipids; D014810:Vitamin E; D007975:Leukotriene B4; D001094:Arachidonate 5-Lipoxygenase