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The effect of vitamin E therapy on plasma and erythrocyte lipid peroxidation in chronic hemodialysis patients
109
Clinica Chimica Acta, 185 (1989) 109-112 Elsevier
CCA 04585
The effect of vitamin E therapy on plasma and erythrocyte lipid peroxidation in chronic hemodialysis patients A. Siiha Yalqin ‘, Mustafa Yurtkuran 2, Kamil Dilek 2, Ahmet Kiliq
I,
Yavuz Taga ’ and Kaya Emerk ’ I Department of Biochemistry, Faculty of Medicine, Marmara University, Istanbul and 2 Department of Internal Medicine, Faculty of Medicine, Uludag University, Bursa (Turkey) (Received 10 February 1989; revision received 10 July 1989, accepted 13 July 1989) Key wor&: Chronic renal failure; Lipid peroxidation; Vitamin E
Summary
The effect of vitamin E therapy on plasma and erythrocyte (RBC) lipid peroxidation was investigated in patients undergoing chronic hemodialysis. Before vitamin E therapy, both plasma and RBC lipid peroxidation values of chronic hemodialysis patients were significantly higher than those of healthy controls. Treatment with vitamin E (300 mg/day) for 1 month resulted in a significant decrease of lipid peroxidation. Vitamin E therapy may be a promising approach to prevent peroxidation of membrane lipids in chronic renal failure.
Introduction
Oxidation of membrane lipids has been implicated in the senescence and breakdown of RBC in various pathological conditions [l-3]. It has been suggested that some metabolic alterations, particularly decreased production of NADPH due to a defect in pentose phosphate pathway activity, lead to accumulation of free radicals and thus increase the susceptibility of RBC to lipid peroxidation in patients with chronic renal failure [4,5]. In addition, several investigators have reported a decrease in the antioxidant capacity of RBC which could contribute to the anemia observed in chronic renal disease [6-S]. Correspondence to: A. Siiha Yalqin, Department University, 81326 Haydarpaga-Istanbul, Turkey. 0009-8981/89/$03.50
of Biochemistry,
Faculty
of Medicine, Marmara
0 1989 Elsevier Science Publishers B.V. (Biomedical Division)
110
Vitamin E is a potent lipid-soluble antioxidant, which has proved to be beneficial in some oxidant-related hemolytic anemias [9,10]. In the present study, we have investigated the protective effect of vitamin E therapy against plasma and RBC lipid peroxidation in patients undergoing chronic hemodialysis. Materials and methods
Twenty chronic renal failure patients undergoing hemodialysis were studied. All patients were dialyzed 3 times weekly, each session lasting 4 h. The dialyses were done with a 0.9-1.3 m2 hollow-fiber dialyzer with an acetate concentration of 38 mEq/l, and a dialysate flow rate of 500 ml/mm. Informed consent to the study was obtained from all patients. The control group consisted of 20 adult healthy individuals. All controls and patients were given a-tocopheryl acetate (300 mg/day) orally for 1 month. Heparinized blood samples were obtained before and after vitamin E treatment. RBC susceptibility to lipid peroxidation was determined by malondialdehyde (MDA) formation, using the addition technique of Stocks et al. [2] in which RBC suspensions were incubated with hydrogen peroxide for 2 h at 37°C. Plasma vitamin E and lipid peroxide (MDA) assays were performed according to Varley et al. [ll] and Yagi [12], respectively. Statistical analyses were carried out with the aid of an Apple Macintosh Plus computer using the program Statview 512 + . Results and discussion
Table I shows the effect of vitamin E therapy on vitamin E and MDA levels in healthy controls and chronic hemodialysis patients. Vitamin E therapy resulted in a
TABLE
I
The effect of vitamn hemodialysis patients Values represent
E therapy
on vitamin
E and lipid peroxide
controls
and chronic
mean If: SEM of 20 determinations. Control
Patients
Before therapy Plasma vitamin (pmoL/l)
levels of healthy
After therapy
Before therapy
After therapy
E
Plasma lipid peroxide (nmol MDA/ml) RBC lipid peroxidation (nmol MDA/g Hb) ’ p < 0.001 compared b p < 0.001 compared
20.7*
1.1
34.7&
2.3 a
21.6k
3.4*
0.2
2.2*
0.1 B
5.6*
160.2 f 18.5 to controls to patients
143.5 f 11.7
before therapy. before therapy.
1.0
0.2 a
602.1 f 48.4 a
33.2+
1.9 Sb
2.5 f
0.1 Sb
225.8 + 28.6 a,b
111
significant increase in plasma vitamin E levels in both groups. Before vitamin E therapy, both plasma and RBC lipid peroxidation values of chronic hemodialysis patients were significantly higher than those of the control group. In the control group, plasma MDA levels and RBC susceptibility to lipid peroxidation values were decreased after therapy, the latter being not significant. Vitamin E therapy resulted in a significant decrease of both plasma MDA levels and RBC susceptibility to lipid peroxidation in chronic hemodialysis patients. Antioxidant effects of high-dose vitamin E have already been reported in some oxidant-related hemolytic anemias and supplemental vitamin E diminished the hemolysis in these patients [9,10]. Similar studies in chronic renal failure patients gave conflicting results [13-X]. The main reason for the controversy is probably the use of either parameters of hemolysis or lipid peroxidation as methods to determine effectiveness of therapy. The results obtained in this study have clearly demonstrated that both plasma MDA levels and RBC susceptibility to lipid peroxidation were significantly decreased in chronic hemodialysis patients after vitamin E therapy. Therefore, vitamin E therapy may be a promising approach to prevent peroxidation of membrane lipids in chronic renal failure. We suggest that the duration of vitamin E therapy should be extended over the life span of RBC to observe significant changes in parameters of hemolysis.
References 1 Chiu D, Lubin B, Shohet SB. Peroxidative reactions in red cell biology. In: Pryor W, ed. Free Radicals in Biology. New York: Academic Press, 1982;115-160. 2 Stocks J, Offerman EL, Model1 CB, Dormandy TL. The susceptibility to autoxidation of human red cell lipids in health and disease. Brit J Haematol 1972;713-724. 3 Kilinq A, Yalvin AS, Yal@n D, Taga Y, Emerk K. Increased erythrocyte susceptibility of lipid peroxidation in human Parkinson’s disease. Neurosci Lett 1988;87:307-310. 4 Yawata Y, Howe R, Jacob HS. Abnormal red cell metabolism causing hemolysis in uremia. Ann Int Med 1973;79:362-367. 5 Giardini 0, Taccone-Gallucci M, Lubrano R, et al. Evidence of red blood cell membrane lipid peroxidation in haemodialysis patients. Nephron 1984;36:235-237. 6 Vanella A, Geremia E, Pinturo R, et al. Superoxide dismutase activity and reduced glutathione content in erythrocytes of uremic patients on chronic dialysis. Acta Haematol 1983;70:312-315. 7 Melissinos KG, Delidou AZ, Varsou AG, Begietti SS, Drivas GJ. Serum and erythrocyte glutathione rcductase activity in chronic renal failure. Nephron 1981;28:76-79. 8 Kqak-Toker N, Yalqin AS, Uysal M. Erythrocyte lipid peroxidation and glutathione peroxidase activities in patients with chronic renal failure. Med Bull Istanbul 1986;19:69-74. 9 Giardini 0, Cantani A, Donfrancesco A. Vitamin E therapy in homozygous beta-thalassemia. New Engl J Med 1981;305:644. 10 Spielberg SP, Boxer LA, Corash LM, Sculman JD. Improved erythrocyte survival with high-dose vitamin E in chronic hemolyzing G6PD and glutathione synthetase deficiencies. Ann Intern Med 1979;90:53-54. 11 Varley H, Gowenlock AH, Bell M. Practical Clinical Biochemistry. Vol. 2, 5th edn. London: William Heinemamr, 1976. 12 Yagi K. Assay for serum lipid peroxide and its clinical significance. In: Yagi K, ed. Lipid Peroxides in Biology and Medicine. New York: Academic Press, 1982;223-242.
112 13 Cohen JD, Viljoen M, Clifford D, DeOliveira AA, Veriava Y, Milne FJ. Plasma vitamin E levels in a chronically hemolyzing group of dialysis patients. Clin Nephrol 1986;25:42-47. 14 Sinsakul V, Drake JR, Lea&t JN, Harrison BR, Kitch CD. Lack of effect of vitamin E therapy on the anemia of patients receiving hemodialysis. Am J Clin Nutr 1984;39:223-226. 15 Giardini 0, Taccone-Gallucci M, Lubrano R, et al. Effects of alpha-tocopherol administration on red blood cell membrane lipid peroxidation in hemodialysis patients. Clin Nephrol 1984;21:174-177.
Clinica Chimica Acta, 185 (1989) 109-112 Elsevier
CCA 04585
The effect of vitamin E therapy on plasma and erythrocyte lipid peroxidation in chronic hemodialysis patients A. Siiha Yalqin ‘, Mustafa Yurtkuran 2, Kamil Dilek 2, Ahmet Kiliq
I,
Yavuz Taga ’ and Kaya Emerk ’ I Department of Biochemistry, Faculty of Medicine, Marmara University, Istanbul and 2 Department of Internal Medicine, Faculty of Medicine, Uludag University, Bursa (Turkey) (Received 10 February 1989; revision received 10 July 1989, accepted 13 July 1989) Key wor&: Chronic renal failure; Lipid peroxidation; Vitamin E
Summary
The effect of vitamin E therapy on plasma and erythrocyte (RBC) lipid peroxidation was investigated in patients undergoing chronic hemodialysis. Before vitamin E therapy, both plasma and RBC lipid peroxidation values of chronic hemodialysis patients were significantly higher than those of healthy controls. Treatment with vitamin E (300 mg/day) for 1 month resulted in a significant decrease of lipid peroxidation. Vitamin E therapy may be a promising approach to prevent peroxidation of membrane lipids in chronic renal failure.
Introduction
Oxidation of membrane lipids has been implicated in the senescence and breakdown of RBC in various pathological conditions [l-3]. It has been suggested that some metabolic alterations, particularly decreased production of NADPH due to a defect in pentose phosphate pathway activity, lead to accumulation of free radicals and thus increase the susceptibility of RBC to lipid peroxidation in patients with chronic renal failure [4,5]. In addition, several investigators have reported a decrease in the antioxidant capacity of RBC which could contribute to the anemia observed in chronic renal disease [6-S]. Correspondence to: A. Siiha Yalqin, Department University, 81326 Haydarpaga-Istanbul, Turkey. 0009-8981/89/$03.50
of Biochemistry,
Faculty
of Medicine, Marmara
0 1989 Elsevier Science Publishers B.V. (Biomedical Division)
110
Vitamin E is a potent lipid-soluble antioxidant, which has proved to be beneficial in some oxidant-related hemolytic anemias [9,10]. In the present study, we have investigated the protective effect of vitamin E therapy against plasma and RBC lipid peroxidation in patients undergoing chronic hemodialysis. Materials and methods
Twenty chronic renal failure patients undergoing hemodialysis were studied. All patients were dialyzed 3 times weekly, each session lasting 4 h. The dialyses were done with a 0.9-1.3 m2 hollow-fiber dialyzer with an acetate concentration of 38 mEq/l, and a dialysate flow rate of 500 ml/mm. Informed consent to the study was obtained from all patients. The control group consisted of 20 adult healthy individuals. All controls and patients were given a-tocopheryl acetate (300 mg/day) orally for 1 month. Heparinized blood samples were obtained before and after vitamin E treatment. RBC susceptibility to lipid peroxidation was determined by malondialdehyde (MDA) formation, using the addition technique of Stocks et al. [2] in which RBC suspensions were incubated with hydrogen peroxide for 2 h at 37°C. Plasma vitamin E and lipid peroxide (MDA) assays were performed according to Varley et al. [ll] and Yagi [12], respectively. Statistical analyses were carried out with the aid of an Apple Macintosh Plus computer using the program Statview 512 + . Results and discussion
Table I shows the effect of vitamin E therapy on vitamin E and MDA levels in healthy controls and chronic hemodialysis patients. Vitamin E therapy resulted in a
TABLE
I
The effect of vitamn hemodialysis patients Values represent
E therapy
on vitamin
E and lipid peroxide
controls
and chronic
mean If: SEM of 20 determinations. Control
Patients
Before therapy Plasma vitamin (pmoL/l)
levels of healthy
After therapy
Before therapy
After therapy
E
Plasma lipid peroxide (nmol MDA/ml) RBC lipid peroxidation (nmol MDA/g Hb) ’ p < 0.001 compared b p < 0.001 compared
20.7*
1.1
34.7&
2.3 a
21.6k
3.4*
0.2
2.2*
0.1 B
5.6*
160.2 f 18.5 to controls to patients
143.5 f 11.7
before therapy. before therapy.
1.0
0.2 a
602.1 f 48.4 a
33.2+
1.9 Sb
2.5 f
0.1 Sb
225.8 + 28.6 a,b
111
significant increase in plasma vitamin E levels in both groups. Before vitamin E therapy, both plasma and RBC lipid peroxidation values of chronic hemodialysis patients were significantly higher than those of the control group. In the control group, plasma MDA levels and RBC susceptibility to lipid peroxidation values were decreased after therapy, the latter being not significant. Vitamin E therapy resulted in a significant decrease of both plasma MDA levels and RBC susceptibility to lipid peroxidation in chronic hemodialysis patients. Antioxidant effects of high-dose vitamin E have already been reported in some oxidant-related hemolytic anemias and supplemental vitamin E diminished the hemolysis in these patients [9,10]. Similar studies in chronic renal failure patients gave conflicting results [13-X]. The main reason for the controversy is probably the use of either parameters of hemolysis or lipid peroxidation as methods to determine effectiveness of therapy. The results obtained in this study have clearly demonstrated that both plasma MDA levels and RBC susceptibility to lipid peroxidation were significantly decreased in chronic hemodialysis patients after vitamin E therapy. Therefore, vitamin E therapy may be a promising approach to prevent peroxidation of membrane lipids in chronic renal failure. We suggest that the duration of vitamin E therapy should be extended over the life span of RBC to observe significant changes in parameters of hemolysis.
References 1 Chiu D, Lubin B, Shohet SB. Peroxidative reactions in red cell biology. In: Pryor W, ed. Free Radicals in Biology. New York: Academic Press, 1982;115-160. 2 Stocks J, Offerman EL, Model1 CB, Dormandy TL. The susceptibility to autoxidation of human red cell lipids in health and disease. Brit J Haematol 1972;713-724. 3 Kilinq A, Yalvin AS, Yal@n D, Taga Y, Emerk K. Increased erythrocyte susceptibility of lipid peroxidation in human Parkinson’s disease. Neurosci Lett 1988;87:307-310. 4 Yawata Y, Howe R, Jacob HS. Abnormal red cell metabolism causing hemolysis in uremia. Ann Int Med 1973;79:362-367. 5 Giardini 0, Taccone-Gallucci M, Lubrano R, et al. Evidence of red blood cell membrane lipid peroxidation in haemodialysis patients. Nephron 1984;36:235-237. 6 Vanella A, Geremia E, Pinturo R, et al. Superoxide dismutase activity and reduced glutathione content in erythrocytes of uremic patients on chronic dialysis. Acta Haematol 1983;70:312-315. 7 Melissinos KG, Delidou AZ, Varsou AG, Begietti SS, Drivas GJ. Serum and erythrocyte glutathione rcductase activity in chronic renal failure. Nephron 1981;28:76-79. 8 Kqak-Toker N, Yalqin AS, Uysal M. Erythrocyte lipid peroxidation and glutathione peroxidase activities in patients with chronic renal failure. Med Bull Istanbul 1986;19:69-74. 9 Giardini 0, Cantani A, Donfrancesco A. Vitamin E therapy in homozygous beta-thalassemia. New Engl J Med 1981;305:644. 10 Spielberg SP, Boxer LA, Corash LM, Sculman JD. Improved erythrocyte survival with high-dose vitamin E in chronic hemolyzing G6PD and glutathione synthetase deficiencies. Ann Intern Med 1979;90:53-54. 11 Varley H, Gowenlock AH, Bell M. Practical Clinical Biochemistry. Vol. 2, 5th edn. London: William Heinemamr, 1976. 12 Yagi K. Assay for serum lipid peroxide and its clinical significance. In: Yagi K, ed. Lipid Peroxides in Biology and Medicine. New York: Academic Press, 1982;223-242.
112 13 Cohen JD, Viljoen M, Clifford D, DeOliveira AA, Veriava Y, Milne FJ. Plasma vitamin E levels in a chronically hemolyzing group of dialysis patients. Clin Nephrol 1986;25:42-47. 14 Sinsakul V, Drake JR, Lea&t JN, Harrison BR, Kitch CD. Lack of effect of vitamin E therapy on the anemia of patients receiving hemodialysis. Am J Clin Nutr 1984;39:223-226. 15 Giardini 0, Taccone-Gallucci M, Lubrano R, et al. Effects of alpha-tocopherol administration on red blood cell membrane lipid peroxidation in hemodialysis patients. Clin Nephrol 1984;21:174-177.