NURTEN ÖZSOY, Ayşe CAN, Özgür MUTLU, NURİYE AKEV, REFİYE YANARDAĞ

Oral zinc supplementation protects rat kidney tissue from oxidative stress in diabetic rats

Çinko (Zn), çok sayıdaki fonksiyonlarının yanı sıra antioksidan özellik de gösteren bir eser elementtir. Bu çalışma, bilimsel kaynaklarda, çinkonun diyabetteki etkisi ile ilgili çelişkili verileri aydınlatmak amacıyla gerçekleştirilmiştir. Swiss albino ırkı dişi sıçanlar 4 gruba ayrılmıştır: Grup I, kontrol; Grup II, kontrol + çinko sülfat, Grup III, streptozotosin (STZ)-diyabetik; Grup IV, STZ-diyabetik + çinko sülfat. Diyabet, intraperitoneal STZ (65 mg/kg) injeksiyonu ile oluşturulmuştur. Çinko sülfat, 60 gün süreyle, her gün 100 mg/kg oranında, gavaj yoluyla Grup II ve IV’e verilmiştir. Deneyin son gününde, sıçanlar anestezi altında kesildikten sonra böbrek dokuları alınarak homojenize edilmiştir. Doku homojenatlarında katalaz (CAT), glutatyon redüktaz (GR), glutatyon peroksidaz (GPx), glutatyon -S-transferaz (GST), superoksit dismütaz (SOD) ve miyeloperoksidaz (MPO) gibi antioksidan enzimlerin aktiviteleri ve protein karbonil miktarı (PCC) saptanmıştır. Ayrıca, böbrek için fonksiyonel bir enzim olan karbonik anhidraz (CA) aktivitesi de tayin edilmiştir. Diyabetik grupta anlamlı olarak değişiklik gösteren antioksidan enzim aktivitelerinin, çinko sülfat ile muamele edilmiş sıçanlarda iyileşme gösterdiği saptanmıştır. Sonuç olarak çinkonun diyabetteki olumlu etkisinin antioksidan etkisi nedeniyle olabileceği ileri sürülmüştür.

Anahtar Kelimeler:

süperoksit dismutaz, çinko, böbrekler, glutatyon transferaz, glutatyon redüktaz (NAD(P)H), glutatyon peroksidaz, enzim aktivitesi, hastalık modelleri, diyabet, katalaz, hayvan modelleri

Ağızdan çinko verilmesi diyabetik sıçanlarda böbrek dokusunu oksidatif hasara karşı korur

Zinc (Zn) is a trace element possessing a wide range of functions and antioxidant properties. This study was undertaken in order to illuminate the conflicting data on the status of zinc in diabetes, present in literature. Female Swiss albino rats were randomly divided into 4 groups: Group I, control; Group II, control + zinc sulfate; Group III, streptozotocin (STZ)-diabetic; Group IV, STZ-diabetic + zinc sulfate. Diabetes was induced by intraperitoneal injection of STZ (65 mg/kg body weight). Zinc sulfate was given daily by gavage at a dose of 100 mg/kg body weight every day for 60 days to Groups II and IV. At the last day of the experiment, rats were killed under anesthesia, kidney tissue was taken and homogenized. Antioxidant enzyme activities such as catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD) and myeloperoxidase (MPO), were determined in tissue homogenates as well as protein carbonyl content (PCC). Carbonic anhydrase (CA) was also determined as a functional enzyme for kidney. It was shown that kidney tissue antioxidant enzyme activities which were significantly impaired in the untreated diabetic group, were reversed in zinc treated diabetic groups, thus showing the beneficial effect of Zn treatment in diabetes via its antioxidant effect.

Keywords:

superoxide dismutase, zinc, kidneys, glutathione transferase, glutathione reductase (NAD(P)H), glutathione peroxidase, enzyme activity, disease models, diabetes, catalase, animal models,

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1. Faure P: Protective effects of antioxidant micronutrients (vitamin E, zinc and selenium) in type 2 diabetes mellitus. Clin Chem Lab Med, 41, 995-998, 2003.
2. Beltramini M, Zambenedetti P, Raso M, Idrissi IbnlKayat M, Zatta P: The effect of Zn(II) and streptozotocin administration in the mouse brain. Brain Res, 1109, 207-218, 2006.
3. Pai LH, Prasad AS: Cellular zinc in patients with diabetes mellitus. Nutr Res, 8, 889-897, 1988.
4. Walter RM, Uriu-Hare JY, Olin KL, Oster MH, Anawalt BD, Critchfield JW, Keen CL: Copper, zinc, manganese, and magnesium status and complications of diabetes mellitus. Diabetes Care, 14, 1050-1056, 1991.
5. Zargar AH, Bashir MI, Masoodi SR, Laway BA, Wani AI, Khan AR, Dar FA: Copper, zinc and magnesium levels in type-1 diabetes mellitus. Saudi Med J, 23, 539-542, 2002.
6. Isbir T, Tamer L, Taylor A, Isbir M: Zinc, copper and magnesium status in insulin-dependent diabetes. Diabetes Res, 26, 41-45, 1994.
7. Roussel AM, Kerkeni A, Zouari N, Mahjoub S, Matheau JM, Anderson RA: Antioxidant effects of zinc supplementation in Tunisians with type 2 diabetes mellitus. J Am Coll Nutr, 22, 316-321, 2003.
8. Adachi Y, Yoshida J, Kodera Y, Kiss T, Jakusch T, Enyedy EA, Yoshikawa Y, Sakurai H: Oral administration of a zinc complex improves type 2 diabetes and metabolic syndromes. Biochem Biophys Res Commun, 351, 165-170, 2006.
9. Yoshikawa Y, Adachi Y, Sakurai H: A new type of orally active anti-diabetic Zn(II)-dithiocarbamate complex. Life Sci, 80, 759-766, 2007.
10. Bolkent S, Yanardag R, Bolkent S, Mutlu O: The influence of zinc supplementation on the pancreas of streptozotocin-diabetic rats. Dig Dis Sci, 54, 2583-2587, 2009.
11. Jansen J, Karges W, Rink L: Zinc and diabetes-clinical links and molecular mechanisms. J Nutr Biochem, 20, 399-417, 2009.
12. Shisheva A, Gefel D, Shechter Y: Insulinlike effects of zinc ion in vitro and in vivo. Preferential effects on desensitized adipocytes and induction of normoglycemia in streptozotocin-induced rats. Diabetes, 41, 982-988, 1992.
13. Sakurai H, Adachi Y: The pharmacology of the insulinomimetic effect of zinc complexes. BioMetals, 18, 319-323, 2005.
14. Meister A: Glutathione metabolism and its selective modification. J Biol Chem, 263, 17205-17208, 1988.
15. Harding JJ, Blakytny R, Ganea E: Glutathione in disease. Biochem Soc Trans, 24, 881-884, 1996.
16. Brown KE, Brunt EM, Heinecke JW: Immunohistochemical detection of myeloperoxidase and its oxidation products in Kupffer cells of human liver. Am J Pathol (AJP), 159, 2081-2088, 2001.
17. Halliwell B, Whiteman M: Measuring reactive species and oxidative damage in vivo and in cell culture: How should you do it and what do the results mean? Brit J Pharmacol, 142, 231-255, 2004.
18. Gambhir KK, Ornasir J, Headings V, Bonar A: Decreased total carbonic anhydrase esterase activity and decreased levels of carbonic anhydrase 1 isozyme in erythrocytes of type II diabetic patients. Biochem Genet, 45, 431-439, 2007.
19. Bülbül A, Bülbül T, Küçükersan S, Şireli M, Eryavuz A: Effects of dietary supplementation of organic and inorganic Zn, Cu and Mn on oxidant/antioxidant balance in laying hens. Kafkas Univ Vet Fak Derg, 14 (1): 19-24, 2008.
20. Yılmaz M, Karapehlivan M, Kaya İ: Effects of zinc sulphate on transcaucasian barb (Capoeta capoeta [Guldenstaedt, 1773]) plasma nitric oxide, malondialdehyde and total sialic acid levels. Kafkas Univ Vet Fak Derg, 18 (1): 61-64, 2012.
21. Rahimi R, Nikfar S, Larijani B, Abdollahi M: A review on the role of antioxidants in the management of diabetes and its complications. Biomed Pharmacother, 59, 365-373, 2005.
22. Aebi H: Catalase in vitro. Methods Enzymol, 105, 121-126, 1984.
23. Carlberg I, Mannervik B: Glutathione reductase. Methods Enzymol, 113, 484-490, 1985.
24. Lawrence RA, Burk RF: Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun, 71, 952-958, 1976.
25. Habig WH, Jakoby WB: Assays for differentation of glutathione-S-transferases. Methods Enzymol, 77, 398-405, 1981.
26. Mylroie AA, Collins H, Umbles C, Kyle J: Erythrocyte superoxide dismutase activity and other parameters of copper status in rats ingesting lead acetate. Toxicol Appl Pharmacol, 82, 512-520, 1986.
27. Hillegass LM, Griswold DE, Brickson B, Albrightson-Winslow C: Assessment of myeloperoxidase activity in whole rat kidney. J Pharmacol Methods, 24, 285-295, 1990.
28. Verpoorte JA, Mehta S, Edsall JT: Esterase activities of human carbonic anhydrases B and C. J Biol Chem, 242, 4221-4229, 1967.
29. Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz A-G, Ahn B-W, Shaltiel S, Stadtman ER: Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol, 186, 464-478, 1990.
30. Reznick AZ, Packer L: Oxidative damage to proteins: Spectro-photometric method for carbonyl assay. Methods Enzymol, 233, 357-363, 1994.
31. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem, 193, 265-275, 1951.
32. Chen MD, Liou SJ, Lin PY, Yang VC, Alexander PS, Lin WH. Effects of zinc supplementation on the plasma glucose level and insulin activity in genetically obese (ob/ob) mice. Biol Trace Elem Res, 61, 303-311, 1998.
33. Kojima Y, Yoshikawa Y, Ueda E, Ueda R, Yamamoto S, Kumekawa K, Yanagihara N, Sakurai H: Insulinomimetic zinc (II) complexes with natural products: In vitro evaluation and blood glucose lowering effect in KK-Ay mice with type 2 diabetes mellitus. Chem Pharm Bull, 51, 1006-1008, 2003.
34. Oteiza PI, Mackenzie GG: Zinc, oxidant-triggered cell signaling, and human health. Mol Aspects Med, 26, 245-255, 2005.
35. Anderson RA, Roussel AM, Zouari N, Mahjoub S, Matheau JM, Kerkeni A: Potential antioxidant effects of zinc and chromium supplementation in people with type 2 diabetes mellitus. J Am Coll Nutr, 20, 212-218, 2001.
36. Ravi K, Ramachandran B, Subramanian S: Protective effect of Eugenia jambolana seed kernel on tissue antioxidants in streptozotocin-induced diabetic rats. Biol Pharm Bull, 27, 1212-1217, 2004.
37. Samman S: Dietary versus cellular zinc: The antioxidant paradox. Free Radical Biol Med, 14, 95-97, 1993.
38. Yanardag R, Tunali S: Vanadyl sulfate administration protects the streptozotocin-induced oxidative damage to brain tissue in rats. Mol Cell Biochem, 286, 153-159, 2006.
39. Gumieniczek A, Hopkała H, Wójtowicz Z, Nikołajuk J: Changes in antioxidant status of heart muscle tissue in experimental diabetes in rabbits. Acta Biochim Pol, 49, 529-535, 2002.
40. Matkovics B, Varga SI, Szabó L, Witas H: The effect of diabetes on the activities of the peroxide metabolism enzymes. Horm Metab Res, 14, 77-79, 1982.
41. Wang G, Zhang L, Li Q: Genetic polymorphisms of GSTT1, GSTM1, and NQO1 genes and diabetes mellitus risk in Chinese population. Biochem Biophys Res Commun, 341, 310-313, 2006.
42. Prasad AS, Bao B, Beck FWJ, Kucuk O, Sarkar FH: Antioxidant effect of zinc in humans. Free Radic Biol Med, 37, 1182-1190, 2004.
43. Cao G, Chen J: Effects of dietary zinc on free radical generation, lipid peroxidation, and superoxide dismutase in trained mice. Arch Biochem Biophys, 291, 147-153, 1991.
44. Roman RM, Wendland AE, Polanczyk CA: Myeloperoxidase and coronary arterial disease: From research to clinical practice. Arq Bras Cardiol, 91, e11-e18, 2007.
45. Maruyama Y, Lindholm B, Stenvinkel P: Inflammation and oxidative stress in ESRD: The role of myeloperoxidase. J Nephrol, 17 Suppl 8, S72-S76, 2004.
46. Bolkent S, Bolkent S, Yanardag R, Mutlu O, Yildirim S: Alterations in somatostatin cells and biochemical parameters following zinc supplementation in gastrointestinal tissue of streptozotocin-induced diabetic rats. Acta Histochem Cytochem, 39, 9-15, 2006.
47. Varghese J, Faith M, Jacob M: Zinc prevents indomethacin-induced renal damage in rats by ameliorating oxidative stress and mitochondrial disfunction. Eur J Pharmacol, 614, 114-121, 2009.
48. Nishita T, Igarashi SI, Asari M: Determination of carbonic anhydrase-III by enzyme-immunoassay in liver, muscle and serum of male rats with streptozotocin-induced diabetes mellitus. Int J Biochem Cell Biol, 27, 359-364, 1995.
49. Dodgson SJ, Contino LC: Rat kidney mitochondrial carbonic anhydrase. Arch Biochem Biophys, 260, 334-341, 1988.
50. Dodgson SJ, Cherian K: Mitochondrial carbonic anhydrase is involved in rat renal glucose synthesis. Am J Physiol, 257, E791–E796, 1989.
51. Sarkar P, Kar K, Mondal MC, Chakraborty I, Kar M: Elevated level of carbonyl compounds correlates with insulin resistance in type 2 diabetes. Ann Acad Med Singapore, 39, 909-912, 2010.
52. Cumaoglu A, Ozansoy G, Irat AM, Aricioglu A, Karasu C, Ari N: Effect of long term, non cholesterol lowering dose of fluvastatin treatment on oxidative stress in brain and peripheral tissues of streptozotocin-diabetic rats. Eur J Pharmacol, 654, 80-85, 2011.