Oxidative stress is associated with increased risk of cardiovascular disease in end-stage renal disease (ESRD) patients. Intravenous (IV) iron has been shown to increase oxidative stress. The aim of the study was to evaluate changes in oxidative stress markers following administration of IV sodium ferric gluconate (SFG) to ESRD patients with and without administration of the antioxidant, α-lipoic acid. This is an open-label, crossover study. 125？mg of IV SFG was administered during control (C) and intervention (I) visits. During the I visit, 600？mg of α-lipoic acid was given orally prior to IV SFG. Blood samples were collected at defined time periods for F2-isoprostane (FIP), lipid hydroperoxide (LHP), malondialdehyde (MDA), and iron indices. We recruited ten African-American ESRD subjects: 50% male; mean age years; mean hemoglobin ？g/dL; ferritin ？ng/mL; transferrin saturation %. There were no significant differences in iron indices between the two visits after IV SFG. MDA, FIP, and LHP increased significantly for both C and I visits with a greater increase in the I group. Administration of IV SFG results in an acute rise in oxidative stress in ESRD patients. In contrast to previous studies, administration of α-lipoic acid was associated with a greater increase in oxidative stress. 1. Introduction Patients with end-stage renal disease (ESRD) on hemodialysis (HD) have very high cardiovascular mortality [1]. Interestingly, the usual risk factors for atherosclerotic diseases in the general population fail to explain the increased cardiovascular mortality in the HD population. For example, unlike the general population, mild-to-moderate elevation of cholesterol or blood pressure does not correlate with increased atherosclerotic complications or mortality in HD patients. As a result, several nontraditional uremia-related risk factors have been considered, including elevated levels of oxidative stress [1, 2]. Intravenous (IV) iron administration has become an integral part of anemia management in ESRD patients; however, exposure to IV iron is among the factors associated with the increase in oxidative stress in the dialysis patients [3–6]. Whether chronic exposure to low maintenance doses of IV iron increases the risk of cardiovascular events has yet to be determined. The oxidative stress markers, malondialdehyde (MDA), lipid hydroperoxide (LHP), and F2 isoprostane (FIP), represent products formed by the reactive oxygen species generated following administration of IV iron. MDA is an end product of peroxidation of polyunsaturated fatty acids and is a
References
[1]
A. S. Levey, J. A. Beto, B. E. Coronado, et al., “Controlling the epidemic of cardiovascular disease in chronic renal disease: what do we know? What do we need to learn? Where do we go from here?” The American Journal of Kidney Diseases, vol. 32, no. 5, pp. 853–906, 1998.
[2]
M. A. Spittle, N. A. Hoenich, G. J. Handelman, R. Adhikarla, P. Homel, and N. W. Levin, “Oxidative stress and inflammation in hemodialysis patients,” The American Journal of Kidney Diseases, vol. 38, no. 6, pp. 1408–1413, 2001.
[3]
R. Agarwal, N. Vasavada, N. G. Sachs, and S. Chase, “Oxidative stress and renal injury with intravenous iron-in patients with chronic kidney disease,” Kidney International, vol. 65, no. 6, pp. 2279–2289, 2004.
[4]
P. S. Lim, Y. H. Wei, Y. L. Yu, and B. Kho, “Enhanced oxidative stress in haemodialysis patients receiving intravenous iron therapy,” Nephrology Dialysis Transplantation, vol. 14, no. 11, pp. 2680–2687, 1999.
[5]
J. M. Roob, G. Khoschsorur, A. Tiran, J. H. Horina, H. Holzer, and B. M. Winklhofer-Roob, “Vitamin E attenuates oxidative stress induced by intravenous iron in patients on hemodialysis,” Journal of the American Society of Nephrology, vol. 11, no. 3, pp. 539–549, 2000.
[6]
D. J. Leehey, D. J. Palubiak, S. Chebrolu, and R. Agarwal, “Sodium ferric gluconate causes oxidative stress but not acute renal injury in patients with chronic kidney disease: a pilot study,” Nephrology Dialysis Transplantation, vol. 20, no. 1, pp. 135–140, 2005.
[7]
D. del Rio, A. J. Stewart, and N. Pellegrini, “A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress,” Nutrition, Metabolism and Cardiovascular Diseases, vol. 15, no. 4, pp. 316–328, 2005.
[8]
A. W. Girotti, “Lipid hydroperoxide generation, turnover, and effector action in biological systems,” Journal of Lipid Research, vol. 39, no. 8, pp. 1529–1542, 1998.
[9]
P. Montuschi, P. J. Barnes, and L. J. Roberts II, “Isoprostanes: markers and mediators of oxidative stress,” The FASEB Journal, vol. 18, no. 15, pp. 1791–1800, 2004.
[10]
K. N. Islam, D. O'Byrne, S. Devaraj, B. Palmer, S. M. Grundy, and I. Jialal, “Alpha-tocopherol supplementation decreases the oxidative susceptibility of LDL in renal failure patients on dialysis therapy,” Atherosclerosis, vol. 150, no. 1, pp. 217–224, 2000.
[11]
E. M. de Cavanagh, L. Ferder, F. Carrasquedo et al., “Higher levels of antioxidant defenses in enalapril-treated versus non- enalapril-treated hemodialysis patients,” The American Journal of Kidney Diseases, vol. 34, no. 3, pp. 445–455, 1999.
[12]
O. Ziouzenkova, L. Asatryan, C. Tetta, M. L. Wratten, J. Hwang, and A. Sevanian, “Oxidative stress during ex vivo hemodialysis of blood is decreased by a novel hemolipodialysis procedure utilizing antioxidants,” Free Radical Biology and Medicine, vol. 33, no. 2, pp. 248–258, 2002.
[13]
G. Clermont, S. Lecour, J. F. Cabanne et al., “Vitamin E-coated dialyzer reduces oxidative stress in hemodialysis patients,” Free Radical Biology and Medicine, vol. 31, no. 2, pp. 233–241, 2001.
[14]
D. Ziegler, H. Nowak, P. Kempler, P. Vargha, and P. A. Low, “Treatment of symptomatic diabetic polyneuropathy with the antioxidant α-lipoic acid: a meta-analysis,” Diabetic Medicine, vol. 21, no. 2, pp. 114–121, 2004.
[15]
K. Marangon, S. Devaraj, O. Tirosh, L. Packer, and I. Jialal, “Comparison of the effect of α-lipoic acid and α-tocopherol supplementation on measures of oxidative stress,” Free Radical Biology and Medicine, vol. 27, no. 9-10, pp. 1114–1121, 1999.
[16]
J. R. Hahm, B. J. Kim, and K. W. Kim, “Clinical experience with thioctacid (thioctic acid) in the treatment of distal symmetric polyneuropathy in Korean diabetic patients,” Journal of Diabetes and Its Complications, vol. 18, no. 2, pp. 79–85, 2004.
[17]
J. Teichert, R. Hermann, P. Ruus, and R. Preiss, “Plasma kinetics, metabolism, and urinary excretion of alpha-lipoic acid following oral administration in healthy volunteers,” Journal of Clinical Pharmacology, vol. 43, no. 11, pp. 1257–1267, 2003.
[18]
J. Teichert, T. Tuemmers, H. Achenbach et al., “Pharmacokinetics of alpha-lipoic acid in subjects with severe kidney damage and end-stage renal disease,” Journal of Clinical Pharmacology, vol. 45, no. 3, pp. 313–328, 2005.
[19]
F. B. Stentz and A. E. Kitabchi, “Palmitic acid-induced activation of human T-lymphocytes and aortic endothelial cells with production of insulin receptors, reactive oxygen species, cytokines, and lipid peroxidation,” Biochemical and Biophysical Research Communications, vol. 346, no. 3, pp. 721–726, 2006.
[20]
F. B. Stentz, G. E. Umpierrez, R. Cuervo, and A. E. Kitabchi, “Proinflammatory cytokines, markers of cardiovascular risks, oxidative stress, and lipid peroxidation in patients with hyperglycemic crises,” Diabetes, vol. 53, no. 8, pp. 2079–2086, 2004.
[21]
R. L. Pisoni, D. S. Fuller, B. A. Bieber, B. W. Gillespie, and B. M. Robinson, “The DOPPS practice monitor for US dialysis care: trends through August 2011,” The American Journal of Kidney Diseases, vol. 60, no. 1, pp. 160–165, 2012.
[22]
A. B. Pai, A. V. Boyd, C. R. McQuade, A. Harford, J. P. Norenberg, and P. G. Zager, “Comparison of oxidative stress markers after intravenous administration of iron dextran, sodium ferric gluconate, and iron sucrose in patients undergoing hemodialysis,” Pharmacotherapy, vol. 27, no. 3, pp. 343–350, 2007.
[23]
J. M. McCord, “Iron, free radicals, and oxidative injury,” Seminars in Hematology, vol. 35, no. 1, pp. 5–12, 1998.
[24]
H. Moini, L. Packer, and N. E. Saris, “Antioxidant and prooxidant activities of α-lipoic acid and dihydrolipoic acid,” Toxicology and Applied Pharmacology, vol. 182, no. 1, pp. 84–90, 2002.
[25]
F. Bhatti, R. W. Mankhey, L. Asico, M. T. Quinn, W. J. Welch, and C. Maric, “Mechanisms of antioxidant and pro-oxidant effects of α-lipoic acid in the diabetic and nondiabetic kidney,” Kidney International, vol. 67, no. 4, pp. 1371–1380, 2005.
[26]
L. Packer, E. H. Witt, and H. J. Tritschler, “Alpha-lipoic acid as a biological antioxidant,” Free Radical Biology and Medicine, vol. 19, no. 2, pp. 227–250, 1995.
[27]
B. C. Scott, O. I. Aruoma, P. J. Evansi et al., “Lipoic and dihydrolipoic acids as antioxidants. A critical evaluation,” Free Radical Research, vol. 20, no. 2, pp. 119–133, 1994.
[28]
Y. J. Suzuki, M. Tsuchiya, and L. Packer, “Antioxidant activities of dihydrolipoic acid and its structural homologues,” Free Radical Research Communications, vol. 18, no. 2, pp. 115–122, 1993.
[29]
A. Childs, C. Jacobs, T. Kaminski, B. Halliwell, and C. Leeuwenburgh, “Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise,” Free Radical Biology and Medicine, vol. 31, no. 6, pp. 745–753, 2001.
