Absent Effect of Zinc Deficiency on the Oxidative Stress of Erythrocytes in Chronic Uremic Rats

Shu-Ming Chen；Ching-Chu Wang；Fanny Lin；Tze-Kong Young

Zinc ； selenium ； antioxidant enzymes ； osmotic fragility ； lipid peroxidation

The Chinese Journal of Physiology

45卷1期（2002 / 03 / 01）

9 - 17

英文

Both anemia and zinc deficiency are commonly observed in patients with chronic uremia. Oxidative stress of red blood cells (RBC) has been suggested to participate in the development of anemia in these patients with chronic uremia due to reduced life span of RBC. Whether zinc deficiency aggravates the effect of oxidative stress on RBC of chronic uremia is still not understood. We thus performed the study to determine the influence of zinc deficiency on the oxidative stress of RBC in uremic rats. Zinc deficiency was induced by long-term dietary zinc deficiency. Five-sixth nephrectomy (5/6 Nx) was used to produce chronic uremia. Experiment was carried out in the following five groups: normal control (NL), chronic uremia (Nx), chronic uremia + dietary zinc deficiency (Nx-D), Nx-D + zinc supplement (Nx-DZ) and Chronic uremia + pair-fed (Nx-PF). Osmotic fragility and lipid peroxidation of RBC were used to evaluate the oxidative stress of RBC. Five weeks after 5/6 nephrectomy (Nx), 5/6 Nx rats present a syndrome of uremia to elevate the levels of plasma creatinine and urea, and reduce the level of plasma zinc (1.12 ± 0.08 vs 1.35 ± 0.05 ug/ml). But they does not find to produce anemia and to increase osmotic fragility and lipid peroxidation in RBC. Dietary zinc deficiency in Nx-D group produced severe anorexia and reduced plasma zinc and selenium levels and the activity of RBC-GPX. Yet in Nx-D rats, osmotic fragility and susceptibility of lipid peroxidation in red cells did not increase, because of the increase of plasma copper level (1.85±0.3 vs 1.41±0.05 ug/ml) and RBC-SOD activity (1.95 ± 0.27 vs 0.78 ± 0.05 unit/g Hb). Zinc supplement in Nx-D rats (Nx-DZ group) recovered the appetite and normalized the levels of plasma zinc, copper and selenium. Food restriction in 5/6 Nx rats (Nx-PF group) decreased plasma copper level and increased osmotic fragility of RBC and elevated the susceptibility of lipid peroxidation after stressing RBC with H2O(subscript r). Because Nx-PF rats presented a lower RBC-SOD activity (0.44±0.11 vs 0.78±0.05 unit/g Hb) and a lower plasma copper level We further found a positive relationship (r=0.802, p＜0.0l) between plasma copper level and RBC-SOD activity in normal and uremic rats. This study suggests that RBC-SOD activity may play an important role in preventing RBC oxidative stress. Plasma copper level may be a marker of RBC-SOD activity. We conclude, in chronic uremia, zinc deficiency doses not result in RBC oxidative stress as plasma copper level is normal, but may affect the absorption of intestinal nutrition.

1. Abdallah, S.M.,Samman, S.(1993).The effect of increasing dietary zinc on the activity of superoxide dismutase and zinc concentration in erythrocytes of healthy female subjects.Eur. J. Clin. Nutr,47,327-332.
2. Aebi, H.,Laszlo, L(1974).Catalase In Methods of Enzymatic Analysis.New York:Academic Press.
3. Bettger, W.,O``Dell, B.L.(1981).A critical physiological role of zinc in the structure and function of biomembranes.Life Sci,28,1425-1438.
4. Bettger, W.J.,Fish, T.J.,O`Dell, B.L.(1978).Effect of copper and zinc status of rats on erythrocyte stability and superoxide dismutase activity.Pro. Soc. Exp. Bio. Med,158,279-282.
5. Bettger, W.J.,O`Dell, B.L.(1993).Physiological role of zinc in the plasma membrane of mammalian cells.J. Nutr. Biochem,4,194-207.
6. Beutler, E.,Williams, W.J.,Beutler E.,Erslev, A.J.,Lichtman, M. A. (eds.)(1990).Osmottic fragility in Hematology.New Tork:Mcgraw-Hill Inc..
7. Blendis, L.M.,Ampil, M.,Wilson, D.R.,Kiwan, J.,Labranche, J.,Johnson, M.,Williams, C.(1981).The importance of dietary protein in the zinc deficiency of uremia.Am. J. Clin. Nutr,34,2658-2661.
8. Bray, T.M.,Bettger, W.J.(1990).The physiological role of zinc as an antioxidant.Free Radic. Bio. Med,8,281-291.
9. Bunk, M.J.,Dnistrian, A.M.,Schwartz, M.K.,Rivlin, R.S.(1989).Dietary zinc deficiency decrease plasma concentrations of vitamin E.. Pro. Soc. Exp. Bio. Med,190,379-384.
10. Canestrari, F.,Galli, F.,Giorgini, A.,Albertini, M.C.,Galiotta, P.,Paseucci, M.,Bossu, M.(1994).Erythrocytes redox state in uremic anemia: Effect of hemodialysis and relevance of glutathione metabolism.Acta. Haematol,91,187-193.
11. Ceballos-Picot, I.,Triver, J.M.,Nicole, A.,Sinet, P.M.,Thevenin, M.(1992).Age-correlated modifications of copper-zinc superoxide dismutase and glutathione related enzyme activities in human erythrocytes.Clin. Chem,38,66-70.
12. Ceballos-Picot, I.,Witko-Sarsat, V.,Merad-Boudia, M.(1996).Glutathione antioxidant system as a marker of oxidative stress in chronic renal failure.Free radical Biol. Med,21,845-853.
13. Chen, S.M.,Chen, T.W.,Young, T.K.(1990).Renal excretion of zinc in patients with chronic uremia.J. Formosan Med. Assoc,89,220-224.
14. Chen, S.M.,Young, T.K.(1996).Effect of paratliyroid hormone on antioxidant enzyme activity and lipid peroxidation of erythrocytes in five-sixths nephrectomized rats.Nephron,73,235-242.
15. Chen, S.M.,Young, T.K.(1998).Effects of zinc deficiency on endogenous antioxidant enzymes and lipid peroxidation in glomerular cells of normal and five-sixths nephrectomized rats.J. Formosan Med. Assoc,97,750-756.
16. Chow, C.K.(1979).Nutritional influences on cellular antioxidant defense systems.Am. J. Clin. Nutr,32,1066-1081.
17. Chvapil, M.,Peng, Y.M.,Aronson, A.L.,Zukoski, C.(1974).Effect of zinc on lipid peroxidation and metal content in some tissues of rats.J. Nutr,104,434-443.
18. Cohen, G.,Dembiec, D.,Marcus, J.(1970).Measurement of catalase activity in tissue extracts.Anal. Biochem,34,30-38.
19. Costagliola, C.,Romano, L.,Sorice, P.,Dibenedetto, A.(1989).Anemia and chronic renal failure: The possible role of the oxidative state of glutathione.Nephron,52,11-14.
20. Desforge, J.F.,Dawson, J.P.(1958).The anemia of renal failure.Arch. Intern. Med,101,326-332.
21. Driscoll, E.R.,Bettger, W.J.(1991).The effect of dietary zinc deficiency on the lipid composition of the rat erythrocyte membrane.Lipids,26,459-467.
22. Durak, I.,Akyol, O.,Basesme, E.,Canbolat, O.,Kavutcu M.(1994).Reduced erythrocyte defense mechanisms against free radical toxicity in patients with chronic renal failure.Nephron,66,76-80.
23. Emenaker, N.J.,Disilvestro, R.A.,Percival, S.(1996).Copper-related blood indexes in kidney dialysis patients.Am. J. Clin. Nutr,64,757-760.
24. Galli, F.,Ronco, C.(2000).Oxidant stress in hemodialysis.Nephron,84,1-5.
25. Gilli, P.,Fagioli, F.,De Paoli Vitali, E.,Farinelli, A.(1985).Is zinc status a problem in the dietary treatment of chronic renal failure.Nephron,40,382.
26. Harris, E.D.(1988).Copper as a cofactor and regulator of copper, zinc superoxide dismutase.J. Nutr,94,508-512.
27. Hasselwander, O.,Young, I.S.(1998).Oxidative stress in chronic renal failure.Free Radic. Res,29,1-11.
28. Hoffman, H.N.,Phyliky, R.L.,Fleming, C.R.(1988).Zinc-induced copper deficiency.Gastroenterology,94,508-512.
29. Ishiyama, A.,Atarashi, K.,Minami, M.,Takagi, M.,Kimura, K.,Goto, A.,Omata, M.(1999).Role of free radicals in the pathogenesis of lipid-induced glomerulosclerosis in rats.Kidney Int,55,1348-1358.
30. Jacob, H.J.,Eaton, J.W.,Yawata, N.Y.(1975).Shortened blood cell survived in uremic patients Beneficial and deleterious effect of dialysis.Kidney Int.
31. Kaplan, J.,O`Halloran, T.V.(1996).Iron metabolism in eukaryotes: Mars and Venus at it again.Science,271,1510-1512.
32. Laurent, B.,Ardaillou, R.(1986).Reactive oxygen species: Production and role in the kidney.Am. J. Physiol,251,765-776.
33. Magnani, M.,Stocchi, V.,Cucchiarini, L.,Chiarantini, L.,Fornaini G.(1986).Red blood cell phagocytosis and lysis following oxidative damage by phenyihydrazine.Cell Biochem. Funct,4,263-269.
34. Mahler, D.J.,Walsh, J.R.,Haynie, G.D.(1971).Magnesium, Zinc and copper in dialysis patients.Am. J. Clin. Pathol,56,17-23.
35. Mc Cord, J.,Fridovich, I.(1969).Superoxide dismutase, An enzymatic function for erythrocuprein.J. Biol. Chem,244,6049-6055.
36. Orsonneau, J.L.,Douet, P.,Massoubre, C.,Lustenberger, P.,Bernard, S.(1989).An improved pyrogallol red-molybdate method for determining total urinary protein.Clin. Chem,35,2233-2236.
37. Osaki, S.,Johnson, D.A.,Frieden, E.(1966).The possible significance of the ferrous oxidase activity of ceruloplasmin in normal human plasma.J. Biol. Chem,241,2746-2751.
38. Paglia, D.,Valentine, W.N.(1967).Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase.J. Lab. Clin. Med.,70,158-169.
39. Park, Y.S.,Suzuki, K.,Taniguchi, N.,Gutteridge, M.C.(1999).Glutathione peroxidase-like activity of ceruloplasmin as an important lung antioxidant.FEBS,458,133-136.
40. Pasaoglu, H.,Muhtaroglu, S.,Gunes, M.,Utas, C.(1996).The role of the oxidative state of glutathione and glutathione-related enzymes in anemia of hemodialysis patients.Clin. Biochem,29,567-572.
41. Peuchant, E.,Carbonneau, M.A.,Dubourg, L.,Thomas, M.J.,Perromat, A.,Vallot, C.,Clerc, M.(1994).Lipoperoxidation in plasma and red blood cells of patients undergoing haemodialysis: Vitamins A, E and iron status.Free Radic. Biol. Med.,16,339-346.
42. Prasad, A.S.(1991).Discovery of human zinc deficiency and studies in an experimental human model.Am. J. Clin. Nutr,53,40-412.
43. Prasad, A.S.(1984).Discovery and importance of zinc in human nutrition.Fed. Proc.,43,2829-2834.
44. Prasad, R.,Nath, R.(1995).Cadmium induced nephrotoxicity in rheusus monkeys (Macaca-mulatta) in relation to protein calorie malnutrition.Toxicology,100,89-100.
45. Samokyszyn, V.M.,Miller, D.M.,Reif D.W.,Aust, S.D.(1989).Inhibition of superoxide and ferritin-dependent lipid peroxidation by ceruloplasmin.J. Biol. Chem.,264,21-26.
46. Schosinsky, K.H.,Lehmann, H.P.,Beeler, M.F.(1974).Measurement of ceruloplasmin from its oxidase activity in serum by use of odianisidine dihydrochloride.Clin. Chem.,20,1556-1563.
47. Shainkin-Kestenbaum, R.,Caruso, C.,Berlyne, G.M.(1990).Reduced superoxide dismutase activity in erythrocytes of dialysis patients: A possible factor in the etiology of uremic anemia.Nephron,55,251-253.
48. Shainkin-kestenbaum, R.,Giatt, Y.,Berlyne, G.M.(1975).The presence and toxicity of guanidinopropionic acid in uremia.Kidney Int,7,302-305.
49. Shaw, A.B.(1967).Haemolysis in chronic renal failure.Br. Med. J.,2,213-216.
50. Shu, K.H.,Lian, J.D.,Yang, Y.F.,Lu, Y.S.,Cheng, C.H.,Chen, D.L.(1987).Plasma zinc level in hemodialysis continuous ambulatory peritoneal dialysis and renal transplantation.J. Formosan Med. Assoc,86,1251-1255.
51. Sohal, R.S.,Weindruch, R.(1996).Oxidative stress, Caloric restriction, and aging.Science,273,59-63.
52. Sondheimer, J.,Mahajan, S.K.,Rye, D.L.,Abu-Hamdan, D.K.,Migdal, S.D.,Prasad, A.S.(1988).Elevated plasma copper in chronic renal failure.Am. J. Clin. Nutr,47,896-899.
53. Stocks, J.,Dormandy, T.L.(1971).The autoxidation of human red cell lipid induced by hydrogen peroxide.Br J. Haematol,20,95-111.
54. Sudesh, K.M.,Ananda, S.P.,Parviz, R.,William, A.B.,Franklin, D.M.(1982).Zinc deficiency: A reversible complication of uremia.Am. J. Clin. Nutr,36,1177-1183.
55. Taneja, B.Y.,Arya, P.(1994).Lipid deposition in intestinal as a possible cause of malabsorption of nutrients in zinc-deficient common carp (Cyprinus carpio).British. J. Nutri,72,753-776.
56. Tetta, C.,Biasioli, S.,Schiavon, R.,Inguaggiato, P.,David, S.,Panichi, V.,Wratten, M.L.(1999).An overview of hemodialysis and oxidative stress.Blood Purif,17,118-126.
57. Tietze, F.(1969).Enzymatic method for quantitative determination of nanogram amounts of total and oxidized glutathione: Applications to mammalian blood and other tissues.Anal. Biochem,27,502-522.
58. Uauy, R.,Olivares, M.,Gonzalez, M.(1998).Essentiality of copper in humans.Am. J. Clin. Nutr.,67,952-959.
59. Wapnir, R.A.(2000).Zinc deficiency, malnutrition and the gastrointestinal tract.J. Nutr.,130,1388-1392.
60. Zumkley, H.,Betram, H.P.,Lison, A.,Knoll, D.,Loss,e H.(1979).Aluminum, zinc and copper concentrations in plasma in chronic renal insufficiency.Clin. Nephrol,12,18-21.