FNS  Vol.3 No.6 , June 2012
Long Term Excessive Zn Supplementation Induced Oxidative Stress in Wistar Rats Fed on Semi-Synthetic Diet
Abstract: The use of Zn as micronutrient in husbandry and agriculture practices and also in baby foods and multivitamin supplements have been increased during the last two decades. However, the effect of long term increasing Zn load on the oxidative stress in the body has not been worked so far. The supplementation of pharmacological dosage of Zn in otherwise Zn adequate diet was investigated with the aim if excess Zn in the diet triggers oxidative stress and its conesquence on enzymes of antioxidant defense system. In this study, three groups of rats were fed on semi-synthetic diet containing 20 mg Zn/kg (control, group-I), 40 mg Zn/kg (group-II) and 80 mg Zn/kg (group-III) diet respectively for a period of 6 months. Blood lipid profile in the serum, lipid peroxidation status and the activities of antioxidant enzymes and trace minerals level were estimated both in the liver and kidney of three groups of rats. The study revealed that the gain in body weight increased in rats in Zn concentration dependent manner. The blood lipid profile displayed a significant rise in serum glucose, total lipids, cholesterol, triglycerides, LDL-cholesterol, VLDL-cholesterol whereas HDL-cholesterol showed a reduction in their levels in group-II and III than their control counter parts. The lipid peroxidation products were higher and the enzyme activities of superoxide dismutase, catalase, glutathione-s-transferase, glutathione reductase, glutathione (reduced) and glucose-6-phosphate dehydrogenase were significantly lowered in liver and kidney of group-II and group-III. Their mineral status revealed a higher Zn concentration and lower Cu, Mg and Mn both in liver and kidney. This data suggest that Zn in excess in diet when fed for longer periods of time induces oxidative stress by altering the status of minerals.
Cite this paper: K. Singh, "Long Term Excessive Zn Supplementation Induced Oxidative Stress in Wistar Rats Fed on Semi-Synthetic Diet," Food and Nutrition Sciences, Vol. 3 No. 6, 2012, pp. 724-731. doi: 10.4236/fns.2012.36098.

[1]   P. Saltman, “Oxidative stress: A Radical View,” Seminars in Hematology, Vol. 26, 1989, pp. 249-256.

[2]   J. M. Mates, Z. C. Perez-Gome, D. Nunez and I. Castro, “Antioxidant Enzymes and Human Diseases,” Clinical Biochemistry, Vol. 32, No. 8, 1999, pp. 595-603. doi:10.1016/S0009-9120(99)00075-2

[3]   M. Kasapoglu and T, Ozben, “Alteration of Antioxidant Enzymes and Oxidative Stress Makers in Aging,” Experimental Gerontology, Vol. 36, 2001, pp. 209-220. doi:10.1016/S0531-5565(00)00198-4

[4]   K. Hirayam and A. Yasutake, “Free Radicals and Trace Elements,” Journal of Trace Elements in Experimental Medicine, Vol. 11, No. 2-3, 1998, pp. 209-217.

[5]   J. R. Prohaska, “Changes in Cu, Zn-Superoxide Dismutase, Cytochrome-C Oxidase, Glutathione Peroxidise and Glutathione Transferase Activities in Copper Deficient Mice and Rats,” Journal of Nutrition, Vol. 121, No. 3, 1991, pp. 355-363.

[6]   G. Paolisso, A. Scheen, F. D’Onofrio and P. Lefebvre, “Magnesium and Glucose Homeostasis,” Diabetologia, Vol. 33, No. 9, 1990, pp. 511-514. doi:10.1007/BF00404136

[7]   D. I. Paynter, “The Role of Dietary Copper, Manganese, Selenium and Vitamin-E in Lipid Peroxidation in Tissue of Rats,” Biological Trace Element Research, Vol. 2, 1980, pp. 121-135. doi:10.1007/BF02798591

[8]   T. M. Bray and W. J. Bettger, “The Physiological Role of Zinc as Antioxidant,” Free Radical Biology and Medicine, Vol. 8, 1990, pp. 281-291. doi:10.1016/0891-5849(90)90076-U

[9]   C. Coudray, M. J. L. Richard, F. Laported, P. Faure, A. M. Roussel and A. E. Favier, “Superoxide Dismutase Activity and Zn Status: A Study in Man and Animals,” Journal of Nutrition, Vol. 3, 1993, pp. 13-26.

[10]   D. Pomp, A. M. Oberbauer and J. D. Murray, “Growth and Body Composition of OMT-la-OGH Transgenic Male Mice with Differing Periods of Transgenic Activation,” Journal of Animal Science, Vol. 70, No. 1, 1992, pp. 198-201.

[11]   S. K. Taneja and R. Mandal, “Assessment of Minerals in Obesity Related Diseases in Chandigarh (India) Population,” Biological Trace Element Research, Vol. 121, No. 2, 2008, pp. 106-123. doi:10.1007/s12011-007-8035-1

[12]   A. B. Abdel-Mageed and F. W. Oehme, “A Review of the Biochemical Roles, Toxicity and Interactions of Zinc, Copper and Iron,” Veterinary and Human Toxicology, Vol. 32, 1990, pp. 34-39.

[13]   J. Aaseth, M. Haugen and O. C. Forre, “Rheumatoid Arthritis and Metal Components—Perspective on the Role of Oxygen Radical Detoxification,” Analyst, Vol. 123, 1998, pp. 3-6. doi:10.1039/a704840h

[14]   J. E. Arsenault and K. H. Brown, “Zn Intake of US Preschool Children Exceeds New Dietary References Intakes,” American Journal of Clinical Nutrition, Vol. 8, 2003, pp. 1011-1016.

[15]   B. Ram, S. P. Garg and S. S. Matharu, “Effect of Contaminants in wastewater on soil and Vegetables—A Case Study,” Panjab Pollution Control Board, 2005.

[16]   K. B. Singh and S. K. Taneja, “Concentration of Zn, Cu and Mn in Vegetables and Meat Foodstuffs Commonly Available in Manipur: A North Eastern State of India,” Electronic Journal of Environmental, Agricultural and Food Chemistry, Vol. 9, No 3, 2010, pp. 610-616.

[17]   D. Oberleas and B. F. Herland, “Phytate Content of Foods: Effect on Dietary Zinc Bioavailability,” Journal of the American Dietetic Association, Vol. 79, 1981, pp. 433436.

[18]   M. C. Orgebincrist, M. Freeman and G. H. Barney, “Sperm Formation in Zn-Deficient Rats,” Annals of Biochem Biophys, Vol. 11, 1971, pp. 547-558. doi:10.1051/rnd:19710403

[19]   P. Roeschlau, E. Bernt and W. A. Gurber, “Enzymatic Determination of Total Cholesterol in Serum,” Journal of Clinical Chemistry & Clinical Biochemistry, Vol. 1974, 1974, pp. 232-266.

[20]   M. W. McGowan, J. D. Artiss, D. R. Stranberg and B. A. Zak, “Peroxide Coupled Method for Colorimetric Determination of Serum Triglycerides,” Clinical Chemistry, Vol. 29, 1983, pp. 438-542

[21]   M. Burstein, H. R. Schonick and R. Morfin, “Rapid Method for the Isolation of Lipoproteins from Human Serum by Precipitation with Polyanions,” Journal of Lipids Research, Vol. 11, 1970, pp. 583-595.

[22]   C. S. Frings and R. T. Dunn, “A Calorimetric Method for Determination of Total Serum Lipids Based on Sulpha-Phosphovanillin Reaction,” American Journal of Clinical Pathology, Vol. 53, 1970, pp. 89-91.

[23]   W. T. Friedewald, R. I. Levy and D. S. Fredrickson, “Estimation of Concentration of LDL-Cholesterol in Plasma without Use of Preparative Ultracentrifuge,” Clinical Chemistry, Vol. 18, No. 6, 1972, pp. 499-502.

[24]   J. A. Beuge and S. D. Aust, “Microsomal Lipid Peroxidation,” Method Enzymology, Vol. 52, 1978, pp. 302-310. doi:10.1016/S0076-6879(78)52032-6

[25]   G. L. Ellman, “Tissue Sulphydryl Groups,” Archives of Biochemistry and Biophysics, Vol. 82, 1959, pp. 70-77. doi:10.1016/0003-9861(59)90090-6

[26]   M. Nishikimi, N. A. Rao and K. Yagi, “The Occurrence of Superoxide Anion in the Reaction of Reduced Phenazine Methosulphate and Molecular Oxygen,” Biochemical and Biophysical Research Communications, Vol. 46, No. 2, 1972, pp. 849-859. doi:10.1016/S0006-291X(72)80218-3

[27]   A. E. Aebi, “Catalase,” In: H. V. Bergnmeyer, Ed., Methods of Enzymatic Analysis, 3rd Edition, Vol. 3, Academic Press, New York, 1983, pp. 273-386.

[28]   W. Habig, M. J. Pabst and W. B. Jackboy, “Glutathione-s-Transfrase. The First Enzymatic Step in Mercapturic Acid Formation,” Journal of Biological Chemistry, Vol. 249, 1974, pp. 7130-7139.

[29]   H. D. Horn, “Glutathione Reductase,” In: H. V. Bergmeyer, Ed., Methods of Enzymatic Analysis, Academic Press, New York, 1971, pp. 875-881.

[30]   G. W. Lohr and H. D. Waller, “Glucose-6-Phosphate Dehydrogenase,” In: H. V. Bergmeyer, Ed., Methods of Enzymatic Analysis, Academic Press, New York, 1963, p. 744.

[31]   O. H. Lowry, N. J. Rosebrough, A. L. Farr and R. J. Randall, “Protein Measurement with the Folin Phenol Reagent,” Journal of Biological Chemistry, Vol. 193, 1951, pp. 265-275.

[32]   S. K. Taneja, R. Mandal and S. Girhotra, “Long Term Excessive Zn Supplementation Promotes Metabolic Syndrome-X in Wistar Rats Fed Sucrose and Fat Rich Semi-Synthetic Diet,” Indian Journal of Experimental Biology, Vol. 44, 2006, pp. 705-718.

[33]   M. D. Chen, P. Y. Lin, V. Cheng and W. H. Lin, “Zinc Supplementation Aggravates Body Fat Accumulation in Genetically Obese Mice and Dietary Obese Mice,” Biological Trace Element Research, Vol. 52, No. 2, 1996, pp. 125-132. doi:10.1007/BF02789454

[34]   A. Prentice, “Does Mild Zn Deficiency Contributes to Poor Growth Performance,” Nutrition Reviews, Vol. 5, 1993, pp. 268-270.

[35]   P. L. Hooper, L. Visconti, P. I. Garry and G. E. Johnson, “Zinc Lowers High Density Lipoprotein Cholesterol Levels,” JAMA, Vol. 244, No. 17, 1980, pp. 1960-1961. doi:10.1001/jama.1980.03310170058030

[36]   R. K. Chandra, “Excessive Intake of Zn Impairs Immune Responses,” JAMA, Vol. 252, No. 11, 1984, pp. 14431446. doi:10.1001/jama.1984.03350110043027

[37]   L. M. Klevay, “The Effect of Zinc to Copper on Cholesterol Metabolism,” American Journal of Clinical Nutrition, Vol. 28, 1975, pp. 764-768.

[38]   N. Y. Yount, D. J. Mc Namara, A. Al-Othman and K. Y. Lei, “The Effect of Copper Deficiency on Rat Hepatic 3 Hydroxy-3 Methylglutaryl Coenzyme—A Reductase Activity,” Journal of Nutritional Biochemistry, Vol. 1, No. 1, 1990, pp. 21-27. doi:10.1016/0955-2863(90)90094-2

[39]   B. W. C. Lau and L. M. Klevay, “Plasma Lecithin: Cholesterol Acyltrasnferase in Copper Deficient Rats,” Journal of Nutrition, Vol. 111, 1981, pp. 1698-1703.

[40]   Y. Rayssiguier and E. Gueux, “Magnesium and Lipids in Cardiovascular Diseases,” Journal of the American College of Nutrition, Vol. 5, 1986, pp. 507-562.

[41]   L. T. Bell and L. S. Hurley, “Ultrastructural Effects of Manganese Deficiency in Liver, Heart, Kidney and Pancreas of Mice,” Lab Invest, Vol. 29, 1973, pp. 723-736.

[42]   R. J. Cousins, “Absorption, Transport and Hepatic Metabolism of Copper and Zinc: Special Reference to Metallothionein and Ceruloplasmin,” Physiological Reviews, Vol. 65, 1985, pp. 238-309.

[43]   J. J. Strain, “Newer Aspects of Micronutrients in Chronic Diseases: Copper,” Proceedings of the Nutrition Society, Vol. 53, No. 3, 1994, pp. 583-598. doi:10.1079/PNS19940067

[44]   P. S. Balevska, E. M. Russanov and T. A. Kasabova, “Studies of Lipid Peroxidation in Rat Liver by Copper Deficiency,” International Journal of Biochemistry, Vol. 13, 1981, pp. 489-493. doi:10.1016/0020-711X(81)90122-1

[45]   M. O. Steinebach and H. T. Wolterbeck, “Effect of Zn on Rat Hepatoma HTC Cells and Primary Cultured Rat Hepatocytes,” Toxicology and Applied Pharmacology, Vol. 118, No. 2, 1993, pp. 245-254. doi:10.1006/taap.1993.1030

[46]   B. Mannervik and U. H. Danielson, “Glutathione-sTransferase-Structure and Catalytic Activity,” Critical Reviews in Biochemistry, Vol. 23, 1988, pp. 283-337. doi:10.3109/10409238809088226

[47]   P. Irato, A. Giacon, R. D. Margo, C. Mestriner and V. Albergoni, “Effect of Zn Supplementation on Metallothionein, Copper and Zinc Concentration in Various Tissues of Copper Loaded Rats,” Biological Trace Element Research, Vol. 51, 1996, pp. 87-95. doi:10.1007/BF02790151