Arachidonate cascade, apoptosis, and vitamin E in peripheral blood mononuclear cells from hemodialysis patients

Mauro Maccarrone, Simone Manca-di-Villahermosa, Carlo Meloni, Renato Massoud, Alberto Mascali, Riccardo Guarina, Alessandro Finazzi-Agrò, Massimo Taccone-Gallucci

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Lipid peroxidation and oxidative stress are enhanced in peripheral blood mononuclear cells (PBMCs) from hemodialysis (HD) patients because of upregulation of the 5-lipoxygenase pathway of the arachidonate cascade. 5-Lipoxygenase activity is specifically inhibited by vitamin E both in vitro and in vivo regardless of its administration route. Methods: The effect of arachidonate cascade enzymes and vitamin E on oxidative stress and apoptosis was investigated in PBMCs from 16 maintenance HD patients treated for at least 6 months with cuprammonium rayon membranes in a two-step crossover study: after a 4-week treatment with vitamin E-coated cuprammonium rayon membranes and again after a 4-week treatment with oral vitamin E. Control PBMCs were obtained from 16 healthy volunteers. Results: Membrane lipoperoxidation, cellular luminescence, membrane fluidity, and leukotriene B4 content were significantly greater in PBMCs from HD patients; lipoxygenase was upregulated, but prostaglandin H synthase (PHS) was not affected. Regardless of administration route, vitamin E partially controlled lipid peroxidation and oxidative stress through direct inhibition of 5-lipoxygenase. Cultured PBMCs from HD patients showed a significant increase in apoptotic cells compared with controls. Vitamin E markedly reduced cell luminescence, membrane fluidity, and apoptosis, whereas the PHS inhibitor indomethacin was ineffective. Similar results were obtained with control PBMCs induced to apoptosis by hydrogen peroxide. Conclusion: Reported data suggest that the 5-lipoxygenase branch of the arachidonate cascade is only responsible for membrane peroxidation, oxidative stress, and apoptosis of PBMCs of HD patients, and administration of vitamin E may be helpful in the control of oxidative stress-related disease in these subjects.

Original languageEnglish
Pages (from-to)600-610
Number of pages11
JournalAmerican Journal of Kidney Diseases
Volume40
Issue number3
DOIs
Publication statusPublished - Sep 2002

Keywords

  • 5-lipoxygenase
  • Apoptosis
  • Cyclooxygenase
  • Hemodialysis (HD)
  • Oxidative stress
  • Peripheral blood mononuclear cells (PBMCs)
  • Vitamin E

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'Arachidonate cascade, apoptosis, and vitamin E in peripheral blood mononuclear cells from hemodialysis patients'. Together they form a unique fingerprint.

Cite this