Biological Effects of Oxidant Stress in Haemodialysis: The Possible Roles of Vitamin E

Abstract

Oxidative stress has been proposed to play a role in many disease states, including cardiovascular and infectious diseases, cancer, diabetes and neurodegenerative pathologies. The fact that these diseases have an increased incidence in uremia, and particularly in dialysis patients, suggests an increased exposure to oxidative stress in this condition. In haemodialysis (HD), the absence of a complete correction of the uremic toxicity together with the untoward effects of the dialysis, malnutrition and the progressive worsening of the clinical condition, can lead to a high susceptibility to oxidative stress by an abnormal production of oxidants – including reactive oxygen species (ROS) and uremic toxins with prooxidant function – and defective antioxidant protection. One of the most investigated biological effects of the oxidative stress in the HD patients is lipid peroxidation in plasma and blood cell membranes. Moreover, we have recently described how abnormal apoptosis in peripheral blood leukocytes is associated with cell oxidative stress (intracellular thiol depletion). Vitamin E, in both in vitro and in vivo conditions, has been proposed to partially correct these effects. In this review we evaluated some features of two new dialysis strategies using an antioxidant approach to the protection against the oxidant stress in HD. Their rationale is based on the emerging role of vitamin E in counteracting some biological effects associated with oxidant stress namely lipid peroxidation and apoptosis. These techniques use: 1) the recirculation of the dialysate through a suspension of vitamin E-enriched liposomes combined with the supplementation by the dialysate with ascorbic acid, this method has been called hemolipodialysis; 2) the coating of the dialysis membrane with vitamin E (vitamin E- modified dialysis membranes). These unconventional approaches to the antioxidant therapy in HD open a widely unexplored and promising field in the evolution of the biomaterials and dialysis quality.

The Effects of Vitamin E-Coated Membrane Dialyzer Compared to Simvastatin in Patients on Chronic Hemodialysis

“…Inclusion criteria were (1) treatment with standard chronic HD for at least 6 months, (2) hypercholesterolemia documented by at least two plasma determinations on fasting condition or indication for hypolipidemic treatment according to 2001 NCEP-ATP III guidelines (primary prevention for patients with a fasting plasma low-density lipoprotein cholesterol (LDL-C) level ! 130 mg/dL and two other risk factors; secondary prevention for patients with a fasting plasma LDL-C level !…”

Oxidative Stress and Cardiovascular Disease in Dialyzed Patients

“…Accelerated atherosclerosis plays an important role in the development of CVD, and there is increasing evidence linking oxidative damage with accelerated atherosclerosis [4, 5, 6, 7, 8]as well as with other complications observed in dialysis patients such as anemia, autoimmune and infectious diseases, and amyloid arthropathy [9, 10, 11, 12]. …”

Oxidant Stress in Hemodialysis

“…From another perspective however, if chemical reactivity of these molecules is not properly controlled and limited, they may become extremely dangerous leading to the oxidative modification of biologically relevant molecules such as lipids, proteins and nucleic acids [2, 4]. Ultimately, a series of acute and chronic responses (damage, repair and adaptation) may arise in tissues and organs, the physiopathological relevance of which has been extensively documented [4, 7]. Oxidative stress has been proposed to play a role in many states often associated with end-stage renal disease, including cardiovascular and infectious diseases, cancer, diabetes, disorders of peripheral and central nervous system, anemia and accelerated aging [1, 2, 3, 4].…”

“…To this immune cell dysfunction may also directly contribute the noxious effects of ROS and the abnormal production of proinflammatory/prooxidant cytokines, particularly TNF-α, one of the most powerful cell death triggers [7]. …”